Autoreactivity -- Holiday STRESS -- Pig CraP - Iodine - Relativity
randall
This one isn't nearly as good as the first one today.
But some of the info may be of help.
http://www.sciencedaily.com/releases/2009/11/091130192930.htm
New Tool in Fight Against Autoimmune Diseases, Blood Cancers
ScienceDaily (Nov. 30, 2009) — A study led by a Scripps Research
Institute scientist describes a new, highly pragmatic approach to the
identification of molecules that prevent a specific type of immune
cells from attacking their host. The findings add a powerful new tool
to the ongoing search for potential treatments for autoimmune
diseases, such as multiple sclerosis (MS), as well as blood cancers,
such as myeloid leukemia.
[and for psoriasis hoPefully :) ]
The study by Thomas Kodadek, a professor in the Chemistry and Cancer
Biology Departments at Scripps Florida, and colleagues was published
in the journal Chemistry & Biology.
In the new study, Kodadek and his colleagues used samples from an
animal model of multiple sclerosis to screen for T cells -- a type of
white blood cell that plays a central role in the immune system --
with a heightened presence in the disease. The screen also identified
molecules that interfere with these T cells' "autoreactivity," in
other words, their attack on the body itself rather than a foreign
invader such as virus or bacteria.
"Our technique simultaneously uncovers and isolates autoreactive T
cells as well as inhibitors to them," Kodadek said. "It's a double
whammy. At the heart of this is a comparative screening process of
normal T cells versus disease-causing T cells. While the process is
technically complicated and difficult, the thinking behind it is not.
We wanted to simplify the process of identifying compounds that could
inhibit autoreactive T cells with exceptional specificity, and we
succeeded."
The scientists used a model of MS, an autoimmune inflammatory disease
affecting the brain and spinal cord, for the study. In MS, the immune
system attacks the myelin sheath covering and protecting nerve cells,
leading to a variety of symptoms depending on which part of the
nervous system is affected. Common symptoms of the condition include
fatigue; numbness; walking, balance, and coordination problems;
bladder and bowel dysfunction; vision problems; dizziness and vertigo;
sexual dysfunction; pain; cognitive problems; emotional changes; and
spasticity.
Simplifying the Process
In setting up the new method to shed light on such autoimmune diseases
and other disorders, Kodadek and his colleagues created a large
collection of peptoids -- molecules related to, but more stable than,
the peptides that make up proteins. By arranging thousands of peptoids
on a microscope slide, the pattern of binding antibodies (a type of
immune molecule) and peptoids can be visualized. By looking at samples
from animal models of a known disease like MS, peptoids that bind to
antibodies closely associated with that disease can be easily
recognized.
Better still, peptoids that bind to autoreactive T cells can be
identified without knowledge of the specific antigen (molecule
triggering the immune attack), providing an unbiased method with which
to search for potentially useful compounds.
Most autoimmune research has focused on finding the disease-causing
antigens first, Kodadek said, a Quixote-like quest that has lasted
more than four decades with little success to show for it.
"With our process, it doesn't really matter what the antigen is," said
Kodadek, a 2006 recipient of the National Institutes of Health
Director's Pioneer Award, which is designed to support individual
scientists of exceptional creativity. "That was really the
breakthrough. We're setting up a system that recognizes T cell
receptors that are very abundant in a sick animal and at low levels in
a healthy animal. Why the abundance? Because that's what making them
sick."
Potential for Therapeutic Discovery
The new process creates new potential for therapeutic discovery.
Molecules that target autoreactive T cells directly, while ignoring
those T cells that recognize foreign antigens, could serve as the
foundation for a novel drug development program aimed at eradicating
autoreactive cells without affecting the normal function of the immune
system.
"Almost without exception, drugs currently used to treat autoimmune
conditions either inhibit something downstream of the autoimmune
response itself, like inflammation, or they moderate the immune system
non-selectively and that results in significant side effects," Kodadek
said.
However, the new study isn't the final answer, according to Kodadek.
He noted that the recent study used a model of MS triggered by a
single antigen. In humans, there could be two -- or two dozen --
antigens triggering an autoimmune disease such as MS. This calls for
further research. The method may be more easily applied to blood
cancers, though, since the disease-causing T cells have been fully
characterized and there are very few of them.
<sniP>
=======================
http://www.sciencedaily.com/releases/2009/11/091130112417.htm
Seeing Family for the Holidays? Scientists Discover How the Stress
Might Kill You
ScienceDaily (Nov. 30, 2009) — If you ever thought the stress of
seeing your extended family over the holidays was slowly killing you
-- bad news: a new research report in the December 2009 print issue of
the Journal of Leukocyte Biology shows that you might be right. Here's
the good news: results from the same study might lead to entirely new
treatments that help keep autoimmune diseases like lupus, arthritis,
and eczema under control.
That's because researchers from the University of Connecticut Health
Center have found that the same part of our nervous system that is
responsible for the fight-or-flight response (called the sympathetic
nervous system) also controls regulatory T cells, which are used by
the body to end an immune response once a foreign invader has been
removed or destroyed.
"We show for the first time that the nervous system controls the
central immune police cells, called regulatory T cells," said Robert
E. Cone, Ph.D., a senior researcher in whose laboratory the work was
done at the University of Connecticut Health Center. "This further
shows that it is imperative to concentrate on the neuro-immune
interactions and to understand how these two different systems, the
immune and nervous systems, interact."
To make this discovery, Cone, Sourojit Bhowmick and colleagues
injected some mice with a drug called 6-hyroxydopamine (6-OHDA) that
selectively removes sympathetic nerves located in different organs, or
a saline solution. Mice injected with 6-OHDA, which effectively
severed the link between the nervous system and the immune system had
twice as many regulatory T cells as the control group in their spleens
and lymph nodes. Further analysis showed that the increase in
regulatory T cells resulted from an increase in a protein called "TGF-
beta," which directs the development and survival of regulatory T
cells.
With this information in hand, Cone and colleagues then sought to see
if 6-OHDA would prevent autoimmune disorders from developing. To do
this, they injected 6-OHDA or a saline solution into mice before
subjecting them and a control group to conditions known to cause an
autoimmune disease similar to multiple sclerosis in humans. Unlike the
control group, the mice treated with 6-OHDA did not develop the
autoimmune disease, showing that not only can the sympathetic nervous
system negatively affect the immune system, but it also shows how it
might be possible to prevent or stop autoimmune disorders.
"Ever since Hans Seyle's groundbreaking work on stress, scientists
have been trying to understand why stressful situations often
exacerbate autoimmune diseases and cause re-emergence of latent
infections," said John Wherry, Ph.D., Deputy Editor of the Journal of
Leukocyte Biology. "In true fight or flight situations, stress can be
a lifesaver, but understanding how the neurological response to the
stress of everyday events such as seeing your family around the
holidays impacts immune responses should provide opportunities for new
therapies."
<sniP>
----
Don't these guys KNOW the MS cure from Dr. Zamboni?
11 hits in the news (recently) for this excess iron and MS theory:
http://news.google.com/news/search?aq=f&pz=1&cf=all&ned=us&hl=en&q=autoimmune+zamboni
=============
It's official now --> if YOU snort pig brain MIST while working the
skull pressure tube at the slaughter house, you risk autoimmune
disease.
http://minnesota.publicradio.org/display/web/2009/11/29/pork-plant-illness/
Psor folks have to much crap in them. Pig brain mist must therefore
have CRAP in it?
Good question....
=============
Why not ramP up the thyroid to move that craP outa your body?
Feel and LOOK good?
While i harP about using iodine to just feel good, it can be used on
your psor NAILs.
http://www.chicagonow.com/blogs/the-mane-attraction/2009/11/white-iodine-for-nail-strength.html
[...]
First I added two almost full droppers of white iodine (yodo blanco
brand) to the bottle (see photo gallery). Then added 2 1/2 dropper of
evoo, 1/2 dropper of Jamaican black castor oil and 5 drops of vitamin
E oil. Tonight will be my second application; the first night I used
straight white iodine I couldn't wait yall, anyway about an hour after
applying the iodine I warmed my evoo concoction and soaked my nails
for 15 minutes. Keep in mind the first week you should apply the
iodine to your naked nails. I'm so excited and can't wait to see the
results! So come on and join me, it would be great to hear what your
results will be as well.
<sniP>
Wow... i want some yodo blanco for my psor nails.
And i use to think all they needed was a vinegar bath.
But was to lazy to get that routine going as a habit.
===========
Getting up to snuff for iodine NEEDs & table salt ain't cutting it?
[...]
“Though the study found that 94 per cent of the UAE population was
consuming iodised salt, it also found that the salt was not adequately
iodised,” said Dr Izzeldin S. Hussein, regional coordinator for
International
Council for Control of Iodine Deficiency Disorders.
The international requirement is 15mg-40mg potassium iodate per
kilogram of salt. The daily required iodine intake through salt for an
adult
is 150mcg.
Iodine is produced by the thyroid gland in our bodies. It helps
maintain a healthy working of the brain and nervous system. Health
complications resulting from iodine deficiency include thyroid gland
dysfunction, including goitre, and various neurologic,
gastrointestinal, and skin abnormalities.
<sniP>
-----
With more iodine a whole population can raise their IQ levels.
Will we all be like Eienstein?
Good question....
==========
Expression of MDC/CCL22 and its receptor CCR4 in rheumatoid arthritis,
psoriatic arthritis and osteoarthritis.
Flytlie HA, Hvid M, Lindgreen E, Kofod-Olsen E, Petersen EL, Jørgensen
A, Deleuran M, Vestergaard C, Deleuran B.
Institute of Medical Microbiology and Immunology, Aarhus University,
DK-8000 Aarhus C, Denmark.
The pathogenesis of rheumatoid arthritis (RA) and psoriatic arthritis
(PsA) involves an abnormal chemokine regulation. The chemokine
receptor CCR4 is necessary for T cell migration to the skin. We,
therefore, studied if CCR4 and its ligand macrophage-derived chemokine
(MDC/CCL22) could participate in spreading the disease between skin
and joints by examining RA, PsA and osteoarthritis (OA) patients. In
synovial fluid from RA and PsA patients we observed a significantly
higher MDC/CCL22 level compared to OA patients. Additionally, the MDC/
CCL22 protein was found to be elevated in RA and PsA plasma compared
to OA and healthy volunteers. Flow cytometry revealed that most CD4(+)
CCR4(+) lymphocytes also co-expressed CD45RO. Neither the MDC/CCL22
level nor the expression of CCR4 correlated to CRP.
Immunohistochemistry of the RA and OA synovial membrane demonstrated
CCR4 to be expressed by mononuclear cells and endothelial cells. Our
results show that MDC/CCL22 is present within the synovial membrane of
RA and OA patients and in high amount in the synovial fluid of
patients with RA and PsA. This will enable migration of CCR4
expressing memory cells supporting that MDC/CCR4 could play a role in
attracting skin specific memory T cells to the joints.
PMID: 19942450
----------
2009 Nov 27. [Epub ahead of print]
Inflammatory Cytokine Tumor Necrosis Factor-alpha Enhances Nerve
Growth Factor Production in Human Keratinocytes, HaCaT Cells.
Takaoka K, Shirai Y, Saito N.
Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe
University, Japan.
The skin lesions of inflammatory skin diseases (e.g., atopic
dermatitis or psoriasis) accompany infiltration of inflammatory cells
like macrophages, where abnormal sensory innervations and elevation of
nerve growth factor (NGF) level are observed. It is thought that
increased NGF mediates the abnormal innervations and this may cause
the hypersensitivity of the skin. However, the mechanism of this
increased NGF production in the skin is still unknown. Here, we show
that tumor necrosis factor (TNF)-alpha, but not interferon-gamma or
interleukin-6, enhanced the NGF production in human keratinocytes. The
enhanced NGF production was abolished by both Raf-1 kinase and MEK
inhibitors, whereas specific inhibitors of p38 mitogen-activated
protein kinase and c-Jun N-terminal kinase did not. The extracellular
signal-regulated kinase (ERK) phosphorylation and expression of NGF
mRNA were accelerated by TNF-alpha treatment. Furthermore, serum was
necessary for the NGF production and epidermal growth factor could
substitute for serum in the effect on NGF secretion. These results
indicate that TNF-alpha enhances NGF production via the Raf-1 / MEK /
ERK pathway in human keratinocytes, suggesting that regulating TNF-
alpha is a therapeutic target to control NGF production and subsequent
sensory innervations.
PMID: 19942804
------------
2009 Nov 23.
AHR activation by tryptophan-pathogenic hallmark of Th17-mediated
inflammation in eosinophilic fasciitis, eosinophilia-myalgia-syndrome
and toxic oil syndrome?
Rieber N, Belohradsky BH.
Children's Hospital, Ludwig-Maximilians-University Munich,
Lindwurmstr. 4, D-80337 Munich, Germany.
The aryl-hydrocarbon-receptor (AHR) is involved as receptor and
transcription factor in dioxin toxicity. Recently, its role in Th17-
mediated autoimmunity and autoinflammation has been described, yet a
disease-associated AHR ligand is still elusive. L-tryptophan and its
metabolites are assumed to trigger the autoinflammatory disorders
eosinophilic fasciitis, eosinophilia-myalgia-syndrome and toxic oil
syndrome. Since L-tryptophan and metabolites are well known as AHR
ligands we hypothesize that it is their interaction with AHR that
induces Th17 cell differentiation and autoinflammation in these
disorders. This, for the first time would link disease-causing
environmental factors to a well-defined cellular receptor and the
subsequent pathogenic pathway.
PMID: 19941898
-----
If they can generate the subsets, why can't we get some Th2? Or is
that to expensive.
But it seems to me i've answered this one before.
Anyway:
Generation of Stable Th1/CTL-, Th2-, and Th17-Inducing Human Dendritic
Cells.
Kalinski P, Wieckowski E, Muthuswamy R, de Jong E.
Departments of Surgery, Immunology, and Infectious Diseases and
Microbiology, University of Pittsburgh and University of Pittsburgh
Cancer Institute, Pittsburgh, PA, USA.
Dendritic cells (DC) are the most potent inducers and regulators of
immune responses, responsible for communication within immune system.
The ability of DC to act both as the inducers of immune responses and
as regulatory/suppressive cells led to the interest in their
immunotherapeutic use in different disease types, ranging from cancer
to autoimmunity, and as a tool to prevent the rejection of
transplanted tissues and organs. Over the last years, several groups
including ours have demonstrated the feasibility of obtaining monocyte-
derived DC with different functions, by modulating the conditions and
the duration of DC maturation. The current chapter provides a detailed
protocol of generating type-1-, type-2-, and type-17-polarized DC for
testing the cytokine-producing abilities of these cells and their
effectiveness in inducing Th1, Th2, and Th17 responses of CD4(+) T
cells and CTL responses of naïve and memory CD8(+) T cells.
PMID: 19941108
----
How come some brave psor researcher isn't checking IL-17 (and thusly
Th17) in the ileum of psoriatics right now?
Maybe they are?
Differential Mucosal IL-17 Expression in Two Gliadin-Induced
Disorders: Gluten Sensitivity and the Autoimmune Enteropathy Celiac
Disease.
Sapone A, Lammers KM, Mazzarella G, Mikhailenko I, Cartenì M, Casolaro
V, Fasano A.
Sezione Biotecnologia e Biologia Molecolare, Dipartimento di Medicina
Sperimentale, Seconda Università degli Studi di Napoli, Naples, Italy.
Background: The immune-mediated enteropathy, celiac disease (CD), and
gluten sensitivity (GS) are two distinct clinical conditions that are
both triggered by the ingestion of wheat gliadin. CD, but not GS, is
associated with and possibly mediated by an autoimmune process. Recent
studies show that gliadin may induce the activation of IL-17-producing
T cells and that IL-17 expression in the CD mucosa correlates with
gluten intake. Methods: The small-intestinal mucosa of patients with
CD and GS and dyspeptic controls was analyzed for expression of IL-17A
mRNA by quantitative RT-PCR. The number of CD3+ and TCR-gammadelta
lymphocytes and the proportion of CD3+ cells coexpressing the Th17
marker CCR6 were examined by in situ small-intestinal
immunohistochemistry. Results: Mucosal expression of IL-17A was
significantly increased in CD but not in GS patients, compared to
controls. This difference was due to enhanced IL-17A levels in >50% of
CD patients, with the remainder expressing levels similar to GS
patients or controls, and was paralleled by a trend toward increased
proportions of CD3+CCR6+ cells in intestinal mucosal specimens from
these subjects. Conclusion: We conclude that GS, albeit gluten-
induced, is different from CD not only with respect to the genetic
makeup and clinical and functional parameters, but also with respect
to the nature of the immune response. Our findings also suggest that
two subgroups of CD, IL-17-dependent and IL-17-independent, may be
identified based on differential mucosal expression of this
cytokine.
PMID: 19940509
--------
Just like with psoriasis, IFB has high Th17 and low Treg's.
I wonder why exactly?
2009 Nov 20. [Epub ahead of print]
Foxp3(+) Regulatory T Cells, Th17 Effector Cells, and Cytokine
Environment in Inflammatory Bowel Disease.
Eastaff-Leung N, Mabarrack N, Barbour A, Cummins A, Barry S.
Department of Gastroenterology and Hepatology, The Queen Elizabeth
Hospital, Woodville South, Adelaide, South Australia, 5011, Australia.
BACKGROUND: Inflammatory bowel disease (IBD) is thought to result from
an aberrant immune response. Inflammation in IBD may be caused by the
loss of homeostasis between CD4(+) CD25(high) Foxp3(+) regulatory
cells (T (reg)) and proinflammatory Th17 cells. The aim of this study
was to investigate T (reg) and Th17 cells in the peripheral blood and
intestinal mucosa of IBD patients and to assess the mucosal cytokine
environment. METHODS: T (reg) and Th17 cells were measured in
peripheral blood of 63 IBD patients and 28 controls by flow cytometry.
Forkhead box p3 (Foxp3), interleukin (IL)-17a, IL-1beta, IL-6, IL-21,
IL-23, and transforming growth factor (TGF)-beta mRNA were analyzed
using real-time reverse transcription polymerase chain reaction in
intestinal biopsies of 24 IBD and 18 control subjects. RESULTS: A
decrease in T (reg) and increase in Th17 cells was observed in the
peripheral blood of IBD patients. When measured in the same patient
and expressed as a ratio, a significant decrease in T (reg)/Th17 ratio
was observed in IBD. Elevated expression of Foxp3, IL-17a, IL-1beta,
and IL-6 was observed in the mucosa of IBD patients, while TGF-beta
was only elevated in ulcerative colitis. CONCLUSION: IBD is associated
with a reduced ratio of T (reg) to Th17 cells in peripheral blood and
is characterized by a proinflammatory cytokine microenvironment, which
supports the continued generation of Th17 cells.
PMID: 19936899
-------
Whats the deferential between early onset male and female psoriatics?
Why?
Look:
Early-onset Crohn Disease Is Associated With Male Sex and a
Polymorphism in the IL-6 Promoter.
Sagiv-Friedgut K, Karban A, Weiss B, Shaoul R, Shamir R, Bujanover Y,
Reif S, Boaz M, Shani I, Levine A, Leshinsky-Silver E.
*Pediatric Gastroenterology Unit, Wolfson Medical Center, Holon
Sackler School of Medicine, Tel Aviv University, Israel
daggerGastroenterology Division, Rambam Medical Center, Haifa, Israel
double daggerPediatric Gastroenterology Units of the Safra Children's
Hospital, Tel Aviv, Sackler School of Medicine, Tel Aviv University,
Israel section signBnei Zion Medical Center, Haifa, Israel paragraph
signMeyer Children's Hospital, Haifa, Sackler School of Medicine, Tel
Aviv University, Israel ||Dana Children's Hospital, Tel-Aviv, Israel
#Epidemiology Unit, Israel **Molecular Biology Laboratory, Wolfson
Medical Center, Holon, Israel.
AIMS:: Pediatric onset of Crohn disease (CD) is characterized by male
sex predominance while adult-onset disease demonstrates female sex
predominance. It has been postulated that this phenomenon may be
genetically determined or due to an effect of estrogen on age of
onset. Interleukin (IL)-6 modulates the TH17 pathway, and the IL-6
promoter is modulated by estrogen, possibly linking genetically
determined inflammation and the presence of estrogen. The aim of our
study was to investigate whether differences in IL-6 promoter genotype
could explain male sex in earlier disease onset. PATIENTS AND
METHODS:: We genotyped 333 patients with CD and 100 controls, 162
pediatric-onset patients (age of onset 18 years and younger) for the
IL-6-174 polymorphic site. Genotype, sex, and age of onset were
compared. RESULTS:: Males with IL-6-174GG genotype (the wild-type
allele) had an increased risk for a younger age of onset compared to
males with IL-6-174GC or CC genotype (G --> C genotype), hazard ratio
(HR) 1.49, P = 0.02, 95% confidence interval (CI) 1.07-2.09. Females
with GG genotype were not found to have an increased risk for a
younger age of onset compared with females with G --> C genotype, HR
1.01, P = 0.96, 95% CI 0.72-1.41. CONCLUSIONS:: Males with IL-6-174GG
genotype are prone to develop CD at a younger age than males with the
IL-6-174G --> C genotype. Our study suggests that age of onset may be
modified by the IL-6-174GG genotype and this modification is sex
dependent. This may be due to increased transcription of IL-6, an
effect that may be repressed by estrogen in females.
PMID: 19934771
So if i'm a male early onset psoriatic is it due to IL-6-->Th17
subset?
=============
2009 Nov 26.
Synergistic effect of TGF-beta superfamily members on the induction of
Foxp3(+) Treg
.
Lu L, Ma J, Wang X, Wang J, Zhang F, Yu J, He G, Xu B, Brand DD,
Horwitz DA, Shi W, Zheng SG.
Division of Rheumatology, Department of Medicine, Keck School of
Medicine, University of Southern California, Los Angeles, CA, USA.
TGF-beta plays an important role in the induction of Treg and
maintenance of immunologic tolerance, but whether other members of TGF-
beta superfamily act together or independently to achieve this effect
is poorly understood. Although others have reported that the bone
morphogenetic proteins (BMP) and TGF-beta have similar effects on the
development of thymocytes and T cells, in this study, we report that
members of the BMP family, BMP-2 and -4, are unable to induce non-
regulatory T cells to become Foxp3(+) Treg. Neutralization studies
with Noggin have revealed that BMP-2/4 and the BMP receptor signaling
pathway is not required for TGF-beta to induce naïve CD4(+)CD25(-)
cells to express Foxp3; however, BMP-2/4 and TGF-beta have a
synergistic effect on the induction of Foxp3(+) Treg. BMP-2/4 affects
non-Smad signaling molecules including phosphorylated ERK and JNK,
which could subsequently promote the differentiation of Foxp3(+) Treg
induced by TGF-beta. Data further advocate that TGF-beta is a key
signaling factor for Foxp3(+) Treg development. In addition, the
synergistic effect of BMP-2/4 and TGF-beta indicates that the
simultaneous manipulation of TGF-beta and BMP signaling might have
considerable effects in the clinical setting for the enhancement of
Treg purity and yield.
PMID: 19943263
====
DC expressing transgene Foxp3 are regulatory APC.
Lipscomb MW, Taylor JL, Goldbach CJ, Watkins SC, Wesa AK, Storkus WJ.
From the Departments of Dermatology.
Tolerogenic dendritic cells (DC) and suppressive Foxp3+ Treg play
important roles in preventing autoimmunity and allograft rejection. We
report that (adenovirus-mediated) ectopic expression of Foxp3 in human
DC (i.e. DC.Foxp3) yields an antigen presenting cell (APC) that severe
limits T cell proliferation and Type 1 immune responses from the
naïve, but not memory, pool of responder T cells in vitro. In marked
contrast, the frequencies of Type-2 and regulatory T cell responses
were dramatically increased after stimulation of naïve T cells with
DC.Foxp3 vs. control DC. DC.Foxp3-induced CD4+CD25+ Treg (XiTreg)
cells potently suppressed the proliferation of, and IFN-gamma
production from, CD4+ and CD8+ responder T cells. Notably, the
immunosuppressive biology of DC.Foxp3 was effectively normalized by
addition of 1-MT or neutralizing anti-TGF-beta1 Ab during the period
of T cell priming. These data suggest the potential utility of
regulatory DC.Foxp3 and/or DC.Foxp3-induced XiTreg as translational
agents for the amelioration or prevention of pathology in the setting
of allograft transplantation and/or autoimmunity. (160 words).
PMID: 19941313
====
You can't have foxy skin with to little foxp3..
2009 Nov 25. [Epub ahead of print]
DC expressing transgene Foxp3 are regulatory APC.
Lipscomb MW, Taylor JL, Goldbach CJ, Watkins SC, Wesa AK, Storkus WJ.
From the Departments of Dermatology.
Tolerogenic dendritic cells (DC) and suppressive Foxp3+ Treg play
important roles in preventing autoimmunity and allograft rejection. We
report that (adenovirus-mediated) ectopic expression of Foxp3 in human
DC (i.e. DC.Foxp3) yields an antigen presenting cell (APC) that severe
limits T cell proliferation and Type 1 immune responses from the
naïve, but not memory, pool of responder T cells in vitro. In marked
contrast, the frequencies of Type-2 and regulatory T cell responses
were dramatically increased after stimulation of naïve T cells with
DC.Foxp3 vs. control DC. DC.Foxp3-induced CD4+CD25+ Treg (XiTreg)
cells potently suppressed the proliferation of, and IFN-gamma
production from, CD4+ and CD8+ responder T cells. Notably, the
immunosuppressive biology of DC.Foxp3 was effectively normalized by
addition of 1-MT or neutralizing anti-TGF-beta1 Ab during the period
of T cell priming. These data suggest the potential utility of
regulatory DC.Foxp3 and/or DC.Foxp3-induced XiTreg as translational
agents for the amelioration or prevention of pathology in the setting
of allograft transplantation and/or autoimmunity. (160 words).
PMID: 19941313
---
Adaptive Treg Generation by DCs and Their Functional Analysis.
Wang L.
Dartmouth Medical School, Norris Cotton Cancer Center, Lebanon, NH,
USA.
Naturally occurring thymus-derived CD4(+)CD25(+)Foxp3(+) regulatory T
cells (nTregs) are critical regulators of immune tolerance. Foxp3(+)
Tregs can also be induced from CD25(-) naïve CD4 T cells in vivo and
ex vivo. This conversion process requires cytokines such as IL2 and
TGFbeta as well as suboptimal TCR stimulation, thus is regulated by
the co-stimulatory status of antigen-presenting cells (i.e., dendritic
cells). Although mature dendritic cells (DCs) are potent initiators of
adaptive immune response, immature steady-state DCs contribute to
immune tolerance. In this chapter, we summarize methods that use ex
vivo splenic DCs to induce the conversion of naïve CD4(+) T cells to
adaptive Foxp3(+)CD4(+) regulatory T cells (aTreg) in the presence of
TGFbeta.
PMID: 19941127
=====================================
What does BIG AL think about GOD?
"Science without religion is lame. Religion without science is
blind."
"I am convinced that He (God) does not play dice."
"God is subtle but he is not malicious."
"God does not care about our mathematical difficulties. He integrates
empirically."
"Whoever undertakes to set himself up as a judge of Truth and
Knowledge is shipwrecked by the laughter of the gods."
"My religion consists of a humble admiration of the illimitable
superior spirit who reveals himself in the slight details we are able
to perceive with our frail and feeble mind."
"A human being is a part of a whole, called by us _universe_, a part
limited in time and space. He experiences himself, his thoughts and
feelings as something separated from the rest... a kind of optical
delusion of his consciousness. This delusion is a kind of prison for
us, restricting us to our personal desires and to affection for a few
persons nearest to us. Our task must be to free ourselves from this
prison by widening our circle of compassion to embrace all living
creatures and the whole of nature in its beauty."
"Not everything that counts can be counted, and not everything that
can be counted counts." (Sign hanging in Einstein's office at
Princeton)
Relativity
"Relativity teaches us the connection between the different
descriptions of one and the same reality".
"I sometimes ask myself how it came about that I was the one to
develop the theory of relativity. The reason, I think, is that a
normal adult never stops to think about problems of space and time.
These are things which he has thought about as a child. But my
intellectual development was retarded,as a result of which I began to
wonder about space and time only when I had already grown up."
"Put your hand on a hot stove for a minute, and it seems like an hour.
Sit with a pretty girl for an hour, and it seems like a minute. THAT'S
relativity."
===============
randall... sit on a hot girls face for an hour... oh wait.. is that
arsebackwards? time is relative and over time
you get more of them....