Genetically restricted cell-mediated cytotoxicity in cattle immune to Theileria parva

Abstract

The protozoan parasite Theileria parva, which is transmitted by the tick Rhipicephalus appendiculatus, produces an acute fatal infection in the lymphoid system of susceptible cattle¹. This disease is a serious constraint to livestock improvement and production in large areas of East Africa¹. The parasite invades host lymphocytes, inducing rapid proliferation followed by widespread lymphocytolysis². Cattle which recover from theileriosis (East Coast fever) spontaneously, or which are immunized by infection and treatment with tetracycline³, are resistant to reinfection with the same isolate of T. parva for at least 3 yr⁴. Immunity against infection with the parasite cannot be ascribed to the production of specific antibodies⁵, but can be transferred adoptively between twins with thoracic duct leukocytes from the immunized partner⁶. These observations suggest that protective immunity is associated with cell-mediated mechanisms. We have now examined the capacity of leukocytes from immune cattle to lyse parasitized lymphoblastoid and non-parasitized tumour cell lines either directly or after stimulation in an autologous mixed lymphocyte reaction (MLR). In contrast to the nonspecific lytic activity of leukocytes from immune cattle reported by Pearson et al.⁷, we describe the sequential appearance in the lymph and blood of immune cattle, of cytotoxic leukocytes with activity restricted to target cells carrying the autologous genotype. These observations suggest that a major component of protective immunity to T. parva is mediated by cytotoxic cells which lyse parasitized cells in a genetically restricted fashion. We have also found that during a primary infection with T. parva cytotoxicity was manifested against allogeneic parasitized cells and xenogeneic uninfected target cells, but not against autologous infected cells. The features of cell-mediated immunity to T. parva during primary infection and immunization are discussed more fully elsewhere⁸.