Cell-mediated responses of immunized vervet monkeys to defined Leishmania T-cell epitopes

Abstract

A population of vervet monkeys was immunized with killed parasites and infected with Leishmania major promastigotes either by needle or by infected-fly bite. The responses of recovered monkeys to mitogens, killed parasites, and molecularly defined T-cell epitopes were then compared with those of control animals. Peripheral blood mononuclear cells (PBMC) from both naive and recovered animals proliferated strongly in response to both B-and T-cell mitogens, although the responses of the recovered animals were less strong than those of the naive animals. Cells from recovered vervets, but not those from naive vervets, also proliferated in response to parasite antigens and synthetic T-cell epitopes. Likewise, cells from recovered animals released gamma interferon and either interleukin 2 (IL-2) or IL-4 into culture media in response to both of the above-mentioned antigens, whereas cells from control animals did not. The fact that no IL-5 could be measured following parasite antigen or synthetic T-cell epitope stimulation of PBMC suggested that cells proliferating in response to these molecules belonged to the Thl 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 CD45RO0 memory cells. The data 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 prime candidates for molecularly defined Leishmania vaccines.

Rhesus monkey model for Leishmania major transmitted by Phlebotomus papatasi sandfly bites

“…Natural transmission of L. major by the bite of sandflies has been accomplished in vervet monkeys by Lawyer et al . (1990) with Phlebotomus duboscqi and by Curry et al . (1994), but those models have not been developed.…”