Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0038002 (
splenomegaly
)
9,873
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The
CD6
lymphocyte receptor has been involved in the pathophysiology of different autoimmune disorders and is now considered a feasible target for their treatment.
In vitro
data show the relevance of
CD6
in the stabilization of adhesive contacts between T-cell and antigen-presenting cells, and the modulation of T-cell receptor signals. However, the
in vivo
consequences of such a function are yet undisclosed due to the lack of suitable genetically modified animal models. Here, the
in vitro
and
in vivo
challenge of
CD6
-deficient (
CD6
-/-
) cells with allogeneic cells was used as an approach to explore the role of
CD6
in immune responses under relative physiological stimulatory conditions. Mixed lymphocyte reaction (MLR) assays showed lower proliferative responses of splenocytes from
CD6
-/-
mice together with higher induction of regulatory T cells (T
reg
, CD4
+
CD25
+
FoxP3
+
) with low suppressive activity on T and B-cell proliferation. In line with these results,
CD6
-/-
mice undergoing a lupus-like disorder induced by chronic graft-versus-host disease (cGvHD) showed higher serum titers of anti-double-stranded DNA and nucleosome autoantibodies. This occurred together with reduced
splenomegaly
, which was associated with lower
in vivo
bromodesoxyuridine incorporation of spleen cells and with increased percentages of spleen follicular B cells (B2, CD21
+
CD23
hi
) and T
reg
cells. Interestingly, functional analysis of
in vivo-
generated
CD6
-/-
T
reg
cells exhibited defective suppressive activity. In conclusion, the data from MLR and cGvHD-induced lupus-like models in
CD6
-/-
mice illustrate the relevance of
CD6
in T (and B) cell proliferative responses and, even more importantly, T
reg
induction and suppressive function in the
in vivo
maintenance of peripheral tolerance.
...
PMID:Relevance of CD6-Mediated Interactions in the Regulation of Peripheral T-Cell Responses and Tolerance. 2861 70
