CYTOTOXICITY IN HUMAN MUCOSAL AND CUTANEOUS LEISHMANIASIS

CD8(+) T cells and lysis of parasitized macrophages seem to be importa nt in the resistance to murine leishmaniasis. in the present study, we evaluated peripheral blood mononuclear cell (PBMC) from patients with either cutaneous (CL) oi mucosal (ML) leishmaniasis in cell lysis ass ays using (51)-Cr-labeled Daudi or K562 cells, or autologous antigen-p ulsed macrophages as targets. Results are reported as lytic units (num ber of cells required for 30% lysis) per million PBMC. Exposure of pat ient PBMC (n = 12) to lysate from Leishmania amazonensis promastigotes led to an increase in cytotoxic activity compared to unstimulated pat ient cells against Daudi (81.8 +/- 14.9 vs 13.6 +/- 5 lytic units (LU) per million PBMC; mean +/- SEM) and K562 (65.7 +/- 8.4 vs 13.1 +/- 5 LU/10(6) PBMC). ML had higher responses than CL in both targets (80.4 +/- 11.0 vs 46.4 +/- 11.6 LU/10(6) PBMC for K562, and 104.3 +/- 23.8 v s 59.3 +/- 14.3 LU/10(6) PBMC for Daudi). Normal control PBMC, stimula ted with L. amazonensis antigen had 6.32 +/- 3.72 LU/10(6) PBMC agains t Daudi cells and 9.06 +/- 2.78 LU/10(6) PBMC against K562. The cell r esponsible for lysis of the K562 cells was characterized as NK, by mea ns of cell separation employing magnetic beads coupled to antibodies. Addition of recombinant TGF-beta or recombinant human IL-10 reduced L. amazonensis-induced cytotoxicity by 90% and 70%, respectively. Cytoto xicity of antigen-stimulated PBMC was also demonstrated against autolo gous L. amazonensis antigen-pulsed macrophages in the range of 6.7 to 41.7 LU/10(6) PBMC. In this system TGF-beta and IL-10 also decreased t he antigen-induced cytotoxic response.