A NON-PROTECTIVE T-HELPER-1 RESPONSE AGAINST THE INTRA-MACROPHAGE PROTOZOAN THEILERIA-ANNULATA

Theileria annulata is a protozoan parasite which infects and transform s bovine macrophages. Infected macrophages possess augmented antigen p resentation capabilities, as they are able to activate the majority of T cells from unexposed animals. In vivo, T cells in the draining lymp h node (principal site of parasite development) are activated 'non-spe cifically' by the parasite. This event is followed by failure of the i mmune response to control the infection. Protective immune responses a gainst intra-macrophage protozoa are usually mediated by T helper 1 (T h1) T cell responses. Here we examine the cytokine responses made by T . annulata-activated T cells. We show that the outcome of in vitro act ivation of T cells by parasitized macrophages is a skewing of their cy tokine responses towards preferential expression of interferon-gamma ( IFN-gamma) mRNA. The in vitro response is mirrored during in vivo infe ction, as greatly elevated amounts of IFN-gamma protein are found in l ymph efferent from infected lymph nodes, while expression of IL-4 mRNA within the node stops. IFN-gamma production does not correlate with p rotection against the parasite, as infected cells flourish during peak IFN-gamma production, and only very small amounts of IFN-gamma are pr oduced during the effective immune response of an immunized animal. Ov erproduction of IFN-gamma and loss of IL-4 expression are also likely to account for the failure of B cells to reach the light zone of germi nal centres, a developmental step which is tightly regulated by cytoki nes.