以組織胞漿菌感染小鼠探討低MHC class II表現對T細胞活化的影響

Abstract

MHC class II molecules are important in positive and negative selections of CD4 T cells in the thymus and are specialized in presenting antigenic peptides to CD4 T cells in the periphery. Engagement of MHCII-peptide complex and TCR is important to CD4 T cell activation. It has been reported that MHC class II deficiency leads to defective CD4 T cell development which in turn results in severe immunodeficiency. Studies on the role of MHC II in immune response have relied mainly on MHC II knockout mice. The question of whether low MHC II expression affects peripheral T cell responses has never been addressed. The availability of ENU-mutagenized mice P235 presents an opportunity to study how low MHC class II expression affects T cell responses to infection. In the present study, I found that T cell responses were reduced in P235 mice after infection with Histoplasma capsulatum (Hc), including both the numbers of activated CD4 and CD8 T cells and the cytokine producing ability of CD4 T cells. The TCR Vβ repertoire in naive P235 mice was not different from that in WT mice. Upon infection by Histoplasma capsulatum, all CD4 and CD8 T cell Vβ populations expanded in P235 mice as well as in WT mice, but the expansion was limited in P235 mice. Interestingly, with lower T cell responses in P235 mice, their ability to clear the fungus at 1/100 of lethal dose was as efficient as in WT mice. Based on the results, it was clear that low MHC II expression reduces T cell responses to infection by Histoplasma capsulatum. The mechanism by which lower T cell responses not affecting fungal clearance still awaits to be investigated.