Protracted Contraction and Memory T Cell Differentiation in Mice Deficient in TNF and Perforin (87.6)

Abstract

Abstract Following infection, pathogen-specific T cells undergo an expansion in numbers followed by contraction to relatively stable memory numbers. Work from others suggests that CD8 T cell responses to infection are altered in mice lacking TNF receptors or perforin. To understand how TNF regulates T cell responses we infected perforin/TNF-double deficient (DKO) mice, perforin-deficient (PKO) mice, and TNF-deficient (TKO) mice with Listeria monocytogenes (LM) and analyzed the MHC Ia-, MHC Ib-, and MHC II-restricted T cell responses. DKO mice exhibited a delay in contraction of MHC Ia- and MHC II-restricted T cells compared to WT mice. All three T cell responses exhibited delayed acquisition of CD62L, a central memory marker, in both DKO and TKO mice. DKO mice have a prolonged infection of LM, however, this did not account for the delay in contraction of the T cell populations, which still occurred in mice treated with antibiotics to eliminate the prolonged infection. These data suggest that TNF and perforin regulate antigen-specific T cell homeostasis, while TNF regulates the phenotype of antigen-specific T cells. Ongoing studies are addressing the mechanisms underlying delayed contraction and whether additional memory characteristics are altered by TNF deficiency.