title: A non-protective T helper 1 response against the intra-macrophage protozoan Theileria annulata.
abstract: 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-gamma) mRNA. The in vitro response is mirrored during in vivo infection, as greatly elevated amounts of IFN-gamma protein are found in lymph efferent from infected lymph nodes, while expression of IL-4 mRNA within the node stops. IFN-gamma production does not correlate with protection against the parasite, as infected cells flourish during peak IFN-gamma production, and only very small amounts of IFN-gamma are produced during the effective immune response of an immunized animal. Overproduction 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 germinal centres, a developmental step which is tightly regulated by cytokines.
authors.affiliation: Division of Molecular Biology, Roslin Institute (Edinburgh), UK.
authors.forename: J D
authors.initials: JD
authors.lastname: Campbell
authors.forename: D J
authors.initials: DJ
authors.lastname: Brown
authors.forename: A K
authors.initials: AK
authors.lastname: Nichani
authors.forename: S E
authors.initials: SE
authors.lastname: Howie
authors.forename: R L
authors.initials: RL
authors.lastname: Spooner
authors.forename: E J
authors.initials: EJ
authors.lastname: Glass
mesh_terms: D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000235:genetics; D008264:Macrophages / Q000469:parasitology*; D008297:Male; D018417:Th1 Cells / Q000502:physiology*; D016796:Theileria annulata / Q000276:immunology*
chemical_list: D015847:Interleukin-4; D007371:Interferon-gamma