Circulating T-follicular helper and type I regulatory T cells have overlapping phenotypes in P. falciparum malaria maintained by parasite exposure

Résumé fourni par la source

Immunity to P. falciparum malaria, develops slowly requiring repeated infection in areas of high transmission and wanes rapidly in the absence of parasite exposure. Antibodies, which are key to this immunity, supported by CD4⁺ T follicular helper (Tfh) cells that, support robust germinal centres. However, in malaria, the parasite-specific CD4⁺ T cell compartment in peripheral blood is dominated by Type 1 regulatory T cells (Tr1), which produce high levels of IL-10 in response to the parasite antigens. And have been linked to clinical immunity, but and delayed parasite clearance. Tr1-like Tfh cells (Tfh10) have been reported in several settings of repeated antigen stimulation but have not been investigated in malaria. We used single-cell RNA sequencing and multiparameter flow cytometry to characterise malaria-specific Tfh and Tr1 cells in a longitudinal cohort of highly exposed Ugandan children and adults and assessed their persistence after transmission interruption. Malaria-specific Tfh and Tr1 cells shared overlapping transcriptional profiles, and Tr1 cell- like transcriptional signatures and phenotypes were detectable within the Tfh cell compartment. These Tfh10 cell subsets were the dominant phenotype of malaria-specific Tfh cells. Following disruption of malaria exposure, the frequencies of malaria-specific Tr1 and Tfh10 cells declined. These findings highlight a close relationship between Tfh and Tr1 cells and show that the Tfh cell compartment in malaria is dominated by Tfh10 cells, associated with to the rapid waning of anti-malaria antibodies.