Effects of Low-Level Persistent Infection on Maintenance of Immunity by CD4 T Cell Subsets and Th1 Cytokines

• Published in: Infection and immunity Vol. 91; no. 3; p. e0053122
• Main Authors: Ibitokou, Samad A, Gbedande, Komi, Opata, Michael M, Carpio, Victor H, Marshall, Karis M, Stephens, Robin
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 15.03.2023
• Subjects: Animals; CD4-Positive T-Lymphocytes; Cytokines - metabolism; Immunology; Interferon-gamma - metabolism; Interleukin-2; Malaria; Mice; Microbial Immunity and Vaccines; Persistent Infection; Reinfection - metabolism; T-Lymphocyte Subsets; Th1 Cells - immunology; T-cell immunity; Th1/Th2 responses; apicomplexan parasites; helper T cell; malaria
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/iai.00531-22

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 Plasmodium chabaudi infection protects the host from reinfection at 2 months postinfection, 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 labeling dividing T cells with 5-bromo-2'-deoxyuridine (BrdU) in infected reporter mice. Large drops in specific T cell numbers and cells upon clearance of parasites 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 expression. In addition, pretreatment of chronically infected animals with neutralizing antibody to interferon gamma (IFN-γ) or with clodronate liposomes before reinfection decreases premunition, supporting a role for Th1-type immunity to reinfection. A pulse-chase experiment comparing chronically infected to treated animals showed that recently divided T cells, particularly IFN-γ TNF IL-2 T cells, are promoted by persistent infection. These data suggest that low-level persistent infection reduces CD4 Tmem and multifunctional Teff survival, but promotes IFN-γ TNF IL-2 T cells and terminally differentiated effector T cells, and prolongs immunity.