CD4+ T cell persistence and function after infection are maintained by low-level peptide:MHC class II presentation.

CD4(+) memory-phenotype T cells decline over time when generated in response to acute infections cleared by other components of the immune system. Therefore, it was of interest to assess the stability of CD4(+) T cells during a persistent Salmonella infection, which is typical of persistent phagocytic infections that are controlled by this lymphocyte subset. We found that CD4(+) T cells specific for Salmonella peptide:MHC class II (MHCII) ligands were numerically stable for >1 y after initial oral infection. This stability was associated with peptide:MHCII-driven proliferation by a small number of T cells in the secondary lymphoid organs that harbored bacteria. The persistent population consisted of multifunctional Th1 cells that induced PD-1 and became exhausted when transferred to hosts expressing the specific peptide:MHCII ligand in all parts of the body. Thus, persistent infection of phagocytes produced a CD4(+) T cell population that was stably maintained by low-level peptide:MHCII presentation.