ADOPTIVE TRANSFER OF IMMUNITY TO THEILERIA-PARVA IN THE CD8(+) FRACTION OF RESPONDING EFFERENT LYMPH

Evidence that class I major histocompatibility complex-restricted cyto toxic T lymphocytes (CTL) are involved in immunity to malaria has high lighted the potential importance of these cells in protection against intracellular parasites. Parasite-specific CTL are a prominent feature of the immune response of cattle to Theileria parva, a related apicom plexan parasite. The relationship between the appearance of these cell s in the blood of immune cattle under challenge and the clearance of i nfection suggests that they are involved in the control of infection, but direct evidence is lacking that CTL can mediate protection. We hav e made a quantitative kinetic study of CTL responses in lymph originat ing from infected lymph nodes in a number of immune cattle under chall enge with T. parva. Direct killing activity and the frequency of CTL p recursors (CTLp) within responding cell populations were evaluated. A substantial increase in the proportion of CD8(+) CTL was observed betw een days 8 and 11 after challenge. Frequencies of CTLp as high as 1:32 were observed and activity was essentially confined to the large blas ting cell fraction. The analogous response in peripheral blood was of lower magnitude and delayed by 1-2 days. The high frequency of CTLp in efferent lymph permitted the adoptive transfer of this activity betwe en immune and naive monozygotic twin calves. In separate experiments, naive calves lethally infected with T. parva were protected by inocula tion of up to 10(10) responding CD8(+) T cells derived from their immu ne twins. Elimination of CD8(+) T cells within the inoculum abrogated this effect. These findings provide direct evidence that CD8(+) T cell s can control T. parva infections in immune cattle.