Protective Anti-Chlamydial Vaccine Regimen-Induced CD4+ T cell Response Mediates Early Inhibition of Pathogenic CD8+ T cell Response Following Genital Challenge.

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.

Meningoencephalitis, Vasculitis, and Abortions Caused by Chlamydia pecorum in a Herd of Cattle.

A cow dairy (n = 2000) in close proximity to a sheep flock had third-trimester abortions and fatalities in cows and calves over a 14-month period. Eighteen of 33 aborted fetuses (55%) had multifocal random suppurative or mononuclear meningoencephalitis with vasculitis. Seventeen of these affected fetuses had intracytoplasmic bacteria in endothelial cells, and 1 fetus with pericarditis had similar bacteria within mesothelial cells or macrophages. Immunohistochemistry for Chlamydia spp. or polymerase chain reaction (PCR) for Chlamydia pecorum or both, performed on brain or pooled tissue, were positive in all 14 tested fetuses that had meningoencephalitis and in 4/4 calves and in 3/4 tested cows that had meningoencephalitis and thrombotic vasculitis. In 1 calf and 11/11 fetuses, C. pecorum PCR amplicon sequences were 100% homologous to published C. pecorum sequences. Enzootic chlamydiosis due to C. pecorum was the identified cause of the late term abortions and the vasculitis and meningoencephalitis in fetuses, calves, and cows. C. pecorum, an uncommon bovine abortogenic agent, is a differential diagnosis in late-term aborted fetuses with meningoencephalitis, vasculitis, and polyserositis.