Effects of Low-level Persistent Infection on maintenance of immunity by CD4 T cell subsets and Th1 cytokines
CD4 T cells are required, along with antibodies, for complete protection from blood-stage infection with Plasmodium spp., which cause malaria. Without continuous exposure, as on emigration of people from endemic areas, protection from malaria decays. As in other persistent infections, low-level P. chabaudi protects the host from re-infection at two months post-infection, a phenomenon termed premunition. Premunition is correlated with T cell responses, rather than antibody levels. We previously showed that while both effector T cells (Teff) and memory T cells (Tmem) are present after infection, Teff protect better than Tmem. Here we studied T cell kinetics post-infection by labelling dividing Ifng+ T cells with BrdU in infected Ifng-reporter mice. A large drop in specific T cell numbers and Ifng+ cells upon clearance of parasite suggest a mechanism for decay of protection. Although protection decays, CD4 Tmem persist, including a highly-differentiated CD27- Effector Memory (Tem) subset that maintains some Ifng expression. In addition, pre-treatment of chronically-infected animals with neutralizing antibody to IFN-{gamma}, or clodronate liposomes before re-infection decrease premonition supporting a role for Th1-type immunity to re-infection. A pulse/chase experiment comparing chronically infected to treated animals showed that recently divided Ifng+ T cells, particularly IFN-{gamma}+TNF+IL-2- T cells, are promoted by persistent infection. These data suggest that low-level persistent infection reduces CD4+ Tmem survival and multi-functional Teff but promotes IFN-{gamma}+TNF+IL-2- Late Effector Memory and Terminally Differentiated Effector T cells and prolongs immunity.