New T Cell Coinhibitory Pathway and Type 1 Diabetes

Project: Research project

Project Details

Description

Immunology T lymphocytes are central mediators of adaptive immunity, playing a key
role in both appropriate immune responses (such as immunity against
pathogens) and abnormal ones (such as autoimmune response that lead to type
1 diabetes). Optimal activation, proliferation, and differentiation to effector
function of T cells require a simultaneous occurrence of two signals: antigen
specific signals via T cell antigen receptors, and additional costimulatory signals
(costimulation) generated mainly by the interaction between the B7 and CD28
families. The intense effort towards understanding T cell costimulation of B7-1,
B7-2/CD28, CTLA-4 pathway over the past decade has shaped much of our
understanding regarding the immune system and immune-related diseases such
as type 1 diabetes. We have discovered the newest member of the B7 family,
B7x, which is capable of inhibiting T cell function in vitro (coinhibition). However,
the role of B7x in diabetes is unknown. Interestingly, we have recently found that,
unlike B7-1 and B7-2, both human and mouse B7x genes are located in insulin-
dependent diabetes loci and are expressed in pancreatic islets. Moreover, we
have found that transgenic mice overexpressing B7x in pancreatic cells are
resistant to CD4 T cell mediated type 1 diabetes. Based on the preliminary data,
we have hypothesized that B7x represents a novel T cell coinhibitory pathway
that attenuates effector T cell function in pancreas. We have generated a number
of important tools (mAbs to B7x, B7x transgenic mice, B7x knock-out mice, etc.)
that provide us with unique opportunities to analyze the role of B7x pathway in
type 1 diabetes. Overall, the studies of this project may not only advance our
understanding of the pathogenic processes underlying type 1 diabetes and its
complicatios but also lead to a rational approach for clinical therapeutic
intervention.
StatusFinished
Effective start/end date9/30/088/31/13

ASJC

  • Medicine(all)