T cell responses to Mycobacterium bovis in red deer, a large animal model for tuberculosis

Red deer (Cervus elaphus) represent an appropriate large animal model to study the immunology of tuberculosis, being naturally susceptible to Mycobacterium bovis infection. Cell-mediated immune responses were investigated in deer displaying protective- or disease-type reactions, following immunization with M. bovis bacille Calmette-Guerin (BCG) or infection with virulent M. bovis, respectively. T cell responses were measured as antigen-dependent cell proliferation and production of T cell growth factor (TCGF) following in vitro stimulation with M. bovis antigens (live or heat-killed BCG, or PPD). T cells from immunized deer proliferated less in response to soluble denatured culture antigen (purified protein derivative, PPD) than to particulate BCG, although there were no differences in the magnitude of these responses between the two groups of animals. Cells derived from immunized deer produced less TCGF than cells from infected deer when stimulated with PPD in vitro, although responses to BCG antigens were similar between the two groups. The majority of TCGF activity was neutralized by anti-IL-2 antibodies, regardless of the animal group or source of antigen used for in vitro stimulation. After 7 days in vitro culture with antigen, blast cells staining positively for alpha beta (CD4, CD8) and gamma delta T cell receptors were recorded. The majority of blasts were CD4+, although in immunized deer fewer CD4+ blasts were produced following in vitro stimulation with PPD than with BCG antigens. These results, together with previous reports from our laboratory, represent the only detailed examinations of T cell responses to M. bovis in this naturally-susceptible ruminant species.