Dynamic changes in cellular immune responses in experimental bovine tuberculosis.

ABSTRACT

BACKGROUND: The development of T-cell responses in natural hosts, such as cattle, would be a useful model of tuberculosis to investigate the changing pattern of T-cell responses and mycobacterial antigens recognized along with the progression of the disease. MATERIAL/METHODS: The present study was undertaken to characterize immune-effector cells and cytokines in Mycobacterium bovis AN5-sensitized cattle, from day 0 to 45 weeks post inoculation (PI). In vitro lymphoproliferation, cytotoxic T lymphocyte (CTL) response, and cytokine release pattern (viz. IL-2, IFN-gamma) from activated PBMC were assessed throughout the spectrum. The effort was made to identify various T-cell target antigens during different post sensitization stages, using T-cell immunoblotting. RESULTS: Cell-mediated immune (CMI) responses were very high between the 9th and 20th week PI. The early appearance of gd+ T-cells was followed by the predominance of CD4+ T-cells, and finally CD8+ T-cells until the 20th week PI. Lymphocyte-effector activity in terms of lymphoproliferation and CTL responses were quite evident between the 9th and 20th weeks PI and around the 12th week PI, respectively. Certain immunodominant polypeptides of culture filtrate preparation of molecular weights 72-74, 30-32, 25 & 22-24 kDa induced higher lymphoproliferation and CTL responses. The kinetics of in vitro cytokine release (IL-2 and IFN-gamma) from PBMC showed a definite trend in all M. bovis AN5-sensitized cattle, with a high concentration between the 9th and 20th weeks PI. CONCLUSIONS: The present investigation revealed some basic aspects of the immune-effector mechanism pertaining to bovine tuberculosis.