23 Although the classification of CD+ve T-cells subsets has expanded to include TH17 and Treg, the TH1/TH2 paradigm has indelibly shaped our understanding cellular immune responses.24 The capability to study cytokine biology and T-cell effector function in sheep find more is improving because of an expanding portfolio of ruminant/ovine-specific immunological reagents.6 However, despite the availability of molecular probes and antibodies to ovine IFN-γ and IL-4, the TH1/TH2 paradigm has never been conclusively
demonstrated in sheep. This has principally been as a result of technical problems in the generation and maintenance of ovine T-cell clones. Furthermore, high variability in cellular immune responses at a polyclonal level in sheep can complicate data interpretation.25 Despite these difficulties, immunological correlates of protection against OEA have been identified at both the cellular and cytokine level and are important steps in our progress towards the development of new and improved disease control measures such as vaccination based on recombinant bacterial components. The knowledge that sheep acquire protective immunity to OEA after abortion
allows targeted dissection of that response (availability of immunological reagents AZD6244 cost permitting). We have previously reported that peripheral blood mononuclear cells (PBMC) from sheep experimentally infected with C. abortus before mid-pregnancy are primed to secrete
IFN-γ (but not IL-4) when mitogenically restimulated in vitro with concanavalin A (Con A). In those studies, the greatest amounts of IFN-γ were found in cultures of PBMC collected from sheep around the time of abortion or in cultures of PBMC collected STK38 from sheep after infection that did not abort, suggestive of a TH1-type protective immune response.21 However, the cellular source of this IFN-γ within the PBMC population has not yet been identified. The functional roles of specific cell subsets in host protection against chlamydial infections have only been conclusively identified to date in congenic mice using adoptive cell transfers, cell depletions or targeted gene knock-outs. However, these resources and techniques are not available in sheep, and thus the relative importance of CD4+ve T cells over other lymphocyte populations for host protection against OEA remains to be fully defined. However, the correlation between IFN-γ production and host immune control of C. abortus infection in sheep is more definitive than the identification of cell subsets producing the IFN-γ.