Differences Between Two Strains of Myelin Basic Protein (MBP) TCR Transgenic Mice: Implications for Tolerance Induction

Abstract

Experimental autoimmune encephalomyelitis (EAE) is mediated by CD4+ T cells which preferentially use the Vβ8.2 TCR in response to myelin basic protein (MBP). Two strains of Tg mice (Vα2.3/Vβ8.2 and Vα4/Vβ8.2) have T cell receptors that recognize the NAc1-11 immunodominant epitope of MBP. We previously reported that oral administration of MBP protects both Vα2.3/Vβ8.2 and Vα4/Vβ8.2 mice from EAE; however, tolerance induction differs between strains and is dependent on the timing of oral antigen. Here we analyze the peripheral and gut-associated lymphoid tissue (GALT) environments of the two strains of Tg mice. Tg cells in the Peyer's patch (PP) but not the spleen of Vα2.3/Vβ8.2 mice demonstrate increased CD69 and decreased CD45RB relative to Vα4/Vβ8.2 mice. High levels of Th1 and Th2 cytokines, proliferative activity and CC chemokines (MCP-1) are observed in the periphery and GALT of Vα2.3/Vβ8.2 Tg mice. In contrast, more non-Tg CD4+ cells are seen in the PP of Vα4/Vβ8.2 mice. These studies suggest that activated Tg T cells and fewer potential regulatory cells in the PP of Vα2.3/Vβ8.2 Tg mice may influence oral tolerance.