DICHOTOMY OF THE T-CELL RESPONSE TO LEISHMANIA ANTIGENS IN PATIENTS SUFFERING FROM CUTANEOUS LEISHMANIASIS - ABSENCE OR SCARCITY OF TH1 ACTIVITY IS ASSOCIATED WITH SEVERE INFECTIONS

The T cell response was studied in 25 patients suffering from cutaneou s leishmaniasis caused by Leishmania major with severe (n = 10) and mi ld (n = 15) disease manifestations. Peripheral blood mononuclear cells (PBMC) from the patients were activated by sonicates of Leishmania pr omastigotes (LMP) and amastigotes (LDA), and the surface protease gp63 . The proliferative responses to Leishmania antigens were lower in pat ients with severe disease than in patients with mild disease (P = 0.01 -0.05), and such a difference was not observed in the response to puri fied protein derivative of tuberculin (PPD) or tetanus toroid (TT). LM P-induced interferon-gamma (IFN-gamma) production was lower in patient s with severe than in patients with mild disease (P < 0.05). When the IL-4 and IFN-gamma responses of each patient were considered, two resp onse patterns were observed in the cultures activated by the Leishmani a sonicates. One response pattern was characterized by high production of IFN-gamma without production of IL-4 (a Th1-like pattern), the oth er was characterized by low IFN-gamma levels which in most cases were associated with IL-4 production (not a Th1-like pattern). These patter ns could not be distinguished when the cells from the same donors were stimulated by TT and PPD. The percentages of patients with a Th1-like response pattern after stimulation by LMP in patients with severe and mild disease manifestations were 30% and 80%, respectively. This diff erence was statistically significant (P = 0.034).