Protective anti-chlamydial vaccine regimen-induced CD4+ T cell response mediates early inhibition of pathogenic CD8+ T cell response following genital challenge

Abstract We have demonstrated previously that TNF-α-producing CD8+ T cells mediate chlamydial pathogenesis, likely in an antigen (Ag)-specific fashion. Here we hypothesize that inhibition of Ag-specific CD8+ T cell response after immunization and/or challenge would correlate with protection against...

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Veröffentlicht in:Pathogens and disease 2024-04, Vol.82
Hauptverfasser: Murthy, Ashlesh K, Wright-McAfee, Erika, Warda, Katerina, Moy, Lindsay N, Bui, Nhi, Musunuri, Tarakarama, Manam, Srikanth, Chako, Clemence Z, Ramsey, Kyle H, Li, Weidang
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Sprache:eng
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Zusammenfassung:Abstract We have demonstrated previously that TNF-α-producing CD8+ T cells mediate chlamydial pathogenesis, likely in an antigen (Ag)-specific fashion. Here we hypothesize that inhibition of Ag-specific CD8+ T cell response after immunization and/or challenge would correlate with protection against oviduct pathology induced by a protective vaccine regimen. Intranasal (i.n.) live chlamydial elementary body (EB), intramuscular (i.m.) live EB, or i.n. irrelevant antigen, bovine serum albumin (BSA), immunized animals induced near-total protection, 50% protection, or no protection, respectively against oviduct pathology following i.vag. C. muridarum challenge. In these models, we evaluated Ag-specific CD8+ T cell cytokine response at various time-periods after immunization or challenge. The results show protective efficacy of vaccine regimens correlated with reduction of Ag-specific CD8+ T cell TNF-α responses following i.vag. chlamydial challenge, not after immunization. Depletion of CD4+ T cells abrogated, whereas adoptive transfer of Ag-specific CD4+ T cells induced the significant reduction of Ag-specific CD8+ T cell TNF-α response after chlamydial challenge. In conclusion, protective anti-chlamydial vaccine regimens induce Ag-specific CD4+ T cell response that mediate early inhibition of pathogenic CD8+ T cell response following challenge and may serve as a predictive biomarker of protection against Chlamydia -induced chronic pathologies. Protective anti-chlamydial vaccine regimens induce Ag-specific CD4+ T cell response that mediates early inhibition of pathogenic CD8+ T cell response following challenge and may serve as a predictive biomarker of protection against Chlamydia -induced chronic pathologies.
ISSN:2049-632X
2049-632X
DOI:10.1093/femspd/ftae008