PARASITE-DRIVEN IN-VITRO HUMAN LYMPHOCYTE CYTOTOXICITY AGAINST AUTOLOGOUS INFECTED MACROPHAGES FROM MUCOSAL LEISHMANIASIS

Parasite-specific cytotoxicity in human leishmaniasis was evaluated in an autologous system. PBL from cutaneous leishmaniasis (CL) or mucosa l leishmaniasis (ML) patients were exposed to Leishmania amazonensis-i nfected autologous macrophages for 7 days and then used as effector ce lls in a cytotoxic assay using Cr-51-labeled autologous infected macro phages as targets, Results are reported as LU per 10(7) PBMC, Cytotoxi c activity is present in ML (9.7 +/- 2.1 LU/10(7) PBMC) but not in CL (1.5 +/- 2.4 LU/10(7) PBMC) patients' lymphocytes, and the differences were highly significant (p < 0.0001). Both CD8(+) T cells and NK cell s exhibited cytotoxic activity, Addition of rIL-12, but not of IFN-gam ma, during the generation of effector cells increased cytotoxic respon ses against infected macrophages. On the other hand, addition of mAb a gainst human IL-12 or lFN-gamma during the stimulation of PBL signific antly decreased the cytotoxic responses, Addition of IL-10 led to dimi nished cytotoxic responses, whereas the addition of anti-IL-10 did not significantly increase the cytotoxic responses. The observation of pa rasite-driven autologous cytotoxic responses in patients with ML, the destructive form of leishmaniasis, but not in CL, suggests that this p henomenon is involved in tissue pathology rather than in protection, U nderstanding the regulation of cytotoxic responses in leishmaniasis ma y be relevant to strategies aimed at limiting pathologic tissue destru ction.