Infection of cattle with Theileria parva induces an early CD8 T cell response lacking appropriate effector function

Abstract

Theileria parva causes an acute lympho-proliferative disease in cattle, which can result in death of susceptible animals within 2–3 weeks of infection. Analyses of the cellular response in the lymph node draining the site of infection demonstrated an early T cell response, with the appearance of large numbers of uninfected lymphoblasts between 6 and 9 days p.i., coinciding with initial detection of parasitised cells. There was a marked increase in the representation of CD8+ T cells and the emergence of a sizable sub-population of CD2− CD8+ α/β T cells during this period. Analysis of T cell receptor β chain variable (TCR BV) gene expression did not reveal any evidence for the involvement of a superantigen in stimulating the response. Responding lymph node cells were found to produce increased quantities of IFNγ and IL-10, and both the CD2+ CD8+ and CD2− CD8+ populations expressed IFNγ transcripts. Purified CD2+ CD8+ cells proliferated when stimulated in vitro with autologous parasitised cells or non-specific mitogens, whereas CD2− CD8+ cells were refractory to these stimuli. In contrast to the parasite-specific cytotoxic activity associated with T cell responses in immune cattle, the responses to primary infection exhibited variable levels of non-specific cytotoxic activity. Stimulation of purified CD2+ CD8+ T cells in vitro with autologous parasitised cells also failed to reveal evidence of specific cytotoxic activity. These findings indicate that primary infection with T. parva induces an aberrant T cell response that lacks appropriate effector activity.