Experimental Myasthenia Gravis in Mice: The role of costimulatory molecules

Abstract

Activation of T-cells requires two signals. One signal is provided by the cognate TCR/MHC-peptide interaction. The second costimulatory signal is mediated through ligation of CD28 by B7 [1]. The CD28 molecule is a 44-kD glycoprotein, which is expressed on all murine and human T cells, while its counter receptor pair B7-1 (CD80) and B7-2 (CD86) are expressed mainly on antigen presenting cells (APCs) [1]. In addition to the conventional signals 1 and 2, a direct signal delivered to T-cells via triggering or cross-linking of the CD40 ligand (CD40L) is also required for full activation of T cells to perform effector functions and to produce cytokines [2]. T-helper cells activate resting B-cells through TCR recognition of MHC class II-peptide complexes and costimulation through CD40L/ CD40 interactions [2]. CD40L is a 33-kDa membrane protein that is preferentially expressed on activated CD4+ T cells [2], while the counter-receptor for CD40L is CD40, expressed on APCs [2]. The mechanisms for CD28 and CD40L in the regulation of the immune system at the cellular and molecular levels are just beginning to be elucidated. Interactions of CD28-B7 and CD40-CD40L have been implicated in T cell-mediated autoimmune diseases such as experimental allergic encephalomyelitis (EAE) and insulin-dependent diabetes mellitus [3-6].