Theileria annulata induces abberrant T cell activation in vitro and in vivo.
The protozoan parasite of cattle, Theileria annulata, causes a severe lymphoproliferative disease, developing initially in the draining lymph node, which is often fatal in naive animals. Infection of macrophages with T. annulata leads to an augmentation of their antigen-presenting capability in vitro and infected cells can induce proliferation of autologous resting T cells from naive animals. This inappropriate activation of T cells may play an important role in the failure of the host to mount an effective immune response in vivo. To investigate this hypothesis we characterized further the response of T cells from naive cattle to infected cells in vitro, and also examined the development of the immune response in lymph nodes draining the sites of T. annulata infection. Both CD4+ and CD8+ T cells from naive peripheral blood mononuclear cells (PBMC) were induced to proliferate and express the activation markers IL-2R and MHC class II when cultured with infected cells. This effect was seen in both 'naive' and 'memory' T cells, and was dependent upon contact with infected cells. In vitro, infected cells are therefore capable of activating T cells irrespective of their antigen specificity or memory status. In draining lymph nodes, although large numbers of IL-2R+ cells developed following infection, these activated cells were only associated with areas of parasite-induced proliferating cells, and subsequently disappeared from the node. Cells expressing IL-2R were not present in recognized sites for T cell development. Germinal centres were severely affected, losing T cell-dependent zones followed by a total destruction of morphology. T cell function is therefore severely disrupted within draining nodes. This study has shown that parasitized cells supply sufficient signals in vitro to activate T cells irrespective of specificity. T cells also are not stimulated in a conventional manner in vivo, and this may play an important role in preventing an effective immune response from being generated.
Division of Molecular Biology, Roslin Institute, UK.
J D
JD
Campbell
S E
SE
Howie
K A
KA
Odling
E J
EJ
Glass
D000818:Animals; D000911:Antibodies, Monoclonal; D002417:Cattle; D002460:Cell Line; D005260:Female; D005434:Flow Cytometry; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology*; D016796:Theileria annulata / Q000276:immunology*; D013801:Theileriasis / Q000276:immunology*
D000911:Antibodies, Monoclonal