THE LEISHMANIA PROMASTIGOTE SURFACE ANTIGEN-2 (PSA-2) IS SPECIFICALLYRECOGNIZED BY TH1 CELLS IN HUMANS WITH NATURALLY ACQUIRED-IMMUNITY TOL-MAJOR

The promastigote surface antigen-2 (PSA-2) is a Leishmania parasite an tigen, which can induce Th1-mediated protection against murine leishma niasis when used as a vaccine. To evaluate PSA-2 as a human vaccine ca ndidate the specific T-cell response to PSA-2 was characterised in ind ividuals immune to cutaneous leishmaniasis, Peripheral blood mononucle ar cells from Sudanese individuals with a past history of self-healing cutaneous leishmaniasis proliferated vigorously in response to PSA-2 isolated from Leishmania major, whereas the antigen did not activate c ells from presumably unexposed Danes. Peripheral blood mononuclear cel ls from individuals with previous L. major infection had varying proli ferative responses to PSA-2 derived from L. donovani promastigotes. Pe ripheral blood mononuclear cells activated by PSA-2 from L. major prod uced high amounts of interferon-gamma and tumour necrosis factor-beta, and little interleukin-4; thereby showing a Th1 cytokine pattern. Par allel cultures showed clear Th1 and Th2 response patterns to purified protein derivative of tuberculin or tetanus toroid, respectively. Flow cytometric analysis revealed that PSA-2 induced blastogenesis in the CD3 positive population and that these cells were the major source of interferon-gamma. The results show that Th1-like cells recognising PSA -2 are expanded during infection by L. major and that they maintain th eir Th1-like cytokine profile upon reactivation in vitro, Since immuni ty to cutaneous leishmaniasis is mediated by antigen-specific Th1-like cells, PSA-2 might be considered a vaccine candidate for human leishm aniasis. (C) 1998 Federation of European Microbiological Societies, Pu blished by Elsevier Science B.V.