Antigen-specific regulatory T cells in bovine paratuberculosis

Mycobacterium avium subspecies paratuberculosis (MAP) is an intracellular pathogen that survives in the hostʹs intestinal macrophages and causes chronic enteritis in ruminants. The subclinical stage of MAP infection is accompanied by loss of pro-inflammatory TH1 response, and a predominant, but ineffective, antibody-mediated TH2 response. How MAP interacts with the bovine immune system and suppresses TH1 responses is unclear. Studies carried out in our lab and others indicate that when peripheral blood mononuclear cells (PBMCs) from subclinical MAP-infected cattle are stimulated with MAP-antigen, IL-10 is up-regulated and leads to suppression of IFN-γ expression in MAP-antigen-reactive effector T cells. IL-10 up-regulation and reduction in IFN-γ would favor MAP survival and proliferation in macrophages. Depletion studies in PBMCs from MAP-infected cattle also revealed that the MAP responsive T-cell population that produces IL-10 is CD4+ and CD25+. Therefore, we hypothesize that cattle infected with MAP develop regulatory T (Treg) cells capable of producing IL-10 that in turn limits peripheral and tissue-specific TH1 immune responses. The aim of this review is to summarize current thinking regarding Treg cells and provide preliminary evidence that infection of cattle with MAP may lead to development of Treg cells.