Rapid proliferation of memory phenotype CD4+ T cells is primarily driven by self-antigens (P1330)

Abstract

Abstract The memory phenotype (MP) CD4+ T cell pool is a heterogeneous population of cells produced upon exposure to foreign antigens and through homeostatic proliferation during transient periods of lymphopenia. Previous studies aimed at identifying the mechanisms regulating the homeostasis of the MP CD4+ T cell pool have shown that a subset of MP CD4+ T cells undergoes a rapid rate of proliferation that is dependent on T cell receptor interactions with peptides bound to MHC-II. However, it is unclear whether the rapidly proliferating MP CD4+ T cells are responding to foreign or self-derived peptide antigens. To address this question, we have analyzed the proliferation of adoptively transferred MP CD4+ T cells in a host which predominantly displays a single self-peptide bound to MHC-II and in germ-free hosts which have a dramatically reduced foreign antigen load. Our results indicate that self-peptide/MHC-II complexes are primarily responsible for driving the rapid proliferation of MP CD4+ T cells in a lymphopenic host. The vigorous response to self-antigens and acquisition of effector functions by the rapidly dividing MP CD4+ T cell subset could potentially play a role in mediating the breakdown in peripheral self-tolerance underlying lymphopenia-associated autoimmune diseases.