CELL-MEDIATED RESPONSES OF IMMUNIZED VERVET MONKEYS TO DEFINED LEISHMANIA T-CELL EPITOPES

A population of vervet monkeys was immunized with killed parasites and infected with Leishmania major promastigotes either by needle or by i nfected-fly bite. The responses of recovered monkeys to mitogens, kill ed parasites, and molecularly defined T-cell epitopes were then compar ed with those of control animals. Peripheral blood mononuclear cells ( PBMC) from both naive and recovered animals proliferated strongly in r esponse to both B- and T-cell mitogens, although the responses of the recovered animals were less strong than those of the naive animals. Ce lls from recovered vervets, but not those from naive vervets, also pro liferated in response to parasite antigens and synthetic T-cell epitop es. Likewise, cells from recovered animals released gamma interferon a nd either interleukin 2 (IL-2) or IL-4 into culture media in response to both of the above-mentioned antigens, whereas cells from control an imals did not. The fact that no IL-5 could be measured following paras ite antigen or synthetic T-cell epitope stimulation of PBMC suggested that cells proliferating in response to these molecules belonged to th e Th1 subset. Phenotypic analysis of the PBMC showed a marked increase in T-cell but not B-cell populations in recovered animals. Among this population was an increased number of CD45R0(+) memory cells. The dat a from this study are in keeping with the earlier finding that vervet monkeys provide an excellent model system for leishmaniasis. Further, these data support the contention that synthetic T-cell epitopes are p rime candidates for molecularly defined Leishmania vaccines.