The Potential Role of Superantigens in the Pathogenesis of Bovine Theileriosis

Theileria parva is an intracellular protozoan parasite that produces an acute and often fatal lymphoproliferative disease (East Coast fever) in susceptible cattle. Studies of experimentally infected cattle have demonstrated a massive increase in the cellularity of the lymph node draining the site of inoculation in the early stages of the infection, when the proportion of parasitized cells in the node was very low. The increased cellularity was associated with a marked increase in the number of lymphoblasts within the node. This suggested that an immune response to the parasite does occur in the regional lymph nodes of naive animals, but is ineffective in controlling the infection. The objective of this study was to characterize the primary immune response in the drainage lymph nodes of cattle infected with T. parva and , in particular, to determine whether or not a superantigen was responsible for inducing lymphocyte activation. Flow cytometric analysis of the phenotype of lymph node cells from infected animals revealed that an unusual CD2-CD8+ subset of alpha/beta T cells formed a major component of the responding population. The appearance of this subset coincided with the initial detection of parasites in the node; the numbers peaked 1-2 days later, and then declined rapidly as the proportion of parasitized cells increased. These cells were refractory to stimulation in vitro, and cells with this phenotype did not participate in the in vitro proliferative response of peripheral blood mononuclear cells from naive animals to autologous parasitized cells. Another interesting feature of the lymph node response in T. parva-infected animals was a large influx of macrophages between days 7 and 9 post-infection. The possibility that a superantigen might be triggering the lymph node response of infected animals was investigated by comparing the TCRBV usage of responding cells with the TCRBV repertoire expressed by normal lymph node T cells. Purified populations of activated T cells and CD2-CD8+ T cells expressed a diverse repertoire of TCRBV genes, which suggests that a superantigen is not involved in the response. In this study a total of 29 new TCRBV gene segments were sequenced, permitting the first detailed classification of bovine TCRBV subfamilies, and revealing that diversification of the TCRBV repertoire in cattle has involved gene duplication events distinct from those of humans and mice.