Negative T cell costimulation and islet tolerance.

Abstract:

:Activation of self-reactive T cells that specifically destroy the pancreatic beta-cells is one of the hallmarks in the development of type 1 diabetes. Thus, for prevention and treatment of this autoimmune disease, approaches to induce and maintain T cell tolerance toward the beta-cells, especially in islet transplantation, have been actively pursued. Noticeably, many of the recent protocols for inducing transplant tolerance involve blockade of positive T cell costimulation extrinsically. Though highly effective in prolonging graft survival, these strategies alone might not be universally sufficient to achieve true tolerance. As the mystery of the suppressive and regulatory T cells unfolds, it is becoming appreciated that exploiting the intrinsic molecular and cellular mechanisms that turn off an immune response would perhaps facilitate the current protocols in establishing T cell tolerance. In this perspective, here we summarize the recent findings on the negative costimulation pathways, in particular, the newly identified PD-1 : PD-L interactions. On the basis of these observations, we propose a new principle of curtailing pathogenic T cell response in which blockade of positive T cell costimulation is reinforced by concurrent engagement of the negative costimulation machinery. Such a strategy may hold greater hope for therapeutic intervention of transplant rejection and autoimmune diseases.

journal_name

Diabetes Metab Res Rev

authors

Gao W,Demirci G,Li XC

doi

10.1002/dmrr.345

keywords:

subject

Has Abstract

pub_date

2003-05-01 00:00:00

pages

179-85

issue

3

eissn

1520-7552

issn

1520-7560

journal_volume

19

pub_type

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