A non‐protective T helper 1 response against the intra‐macrophage protozoan Theileria annulata

Theileria annulata is a protozoan parasite which infects and transforms bovine macrophages. Infected macrophages possess augmented antigen presentation capabilities, as they are able to activate the majority of T cells from unexposed animals. In vivo , T cells in the draining lymph node (principal site of parasite development) are activated ‘non‐specifically’ by the parasite. This event is followed by failure of the immune response to control the infection. Protective immune responses against intra‐macrophage protozoa are usually mediated by T helper 1 (Th1) T cell responses. Here we examine the cytokine responses made by T. annulata ‐activated T cells. We show that the outcome of in vitro activation of T cells by parasitized macrophages is a skewing of their cytokine responses towards preferential expression of interferon‐gamma (IFN‐γ) mRNA. The in vitro response is mirrored during in vivo infection, as greatly elevated amounts of IFN‐γ protein are found in lymph efferent from infected lymph nodes, while expression of IL‐4 mRNA within the node stops. IFN‐γ production does not correlate with protection against the parasite, as infected cells flourish during peak IFN‐γ production, and only very small amounts of IFN‐γ are produced during the effective immune response of an immunized animal. Overproduction of IFN‐γ and loss of IL‐4 expression are also likely to account for the failure of B cells to reach the light zone of germinal centres, a developmental step which is tightly regulated by cytokines.