Effects of Low-Level Persistent Infection on Maintenance of Immunity by CD4 T Cell Subsets and Th1 Cytokines
| Autor: | Samad A. Ibitokou, Komi Gbedande, Michael M. Opata, Victor H. Carpio, Karis M. Marshall, Robin Stephens |
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| Rok vydání: | 2023 |
| Předmět: | |
| Zdroj: | Infection and Immunity. 91 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.00531-22 |
| Popis: | CD4 T cells are required, along with antibodies, for complete protection from blood-stage infection withPlasmodium 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-levelP. chabaudiprotects 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 dividingIfng+T cells with BrdU in infectedIfng-reporter mice. A large drop in specific T cell numbers andIfng+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 someIfngexpression. In addition, pre-treatment of chronically-infected animals with neutralizing antibody to IFN-γ, 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 dividedIfng+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 survival and multi-functional Teff but promotes IFN-γ+TNF+IL-2-Late Effector Memory and Terminally Differentiated Effector T cells and prolongs immunity. |
| Databáze: | OpenAIRE |
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