T-CELL RESPONSES TO INFECTED AUTOLOGOUS MONOCYTES IN PATIENTS WITH CUTANEOUS AND MUCOCUTANEOUS LEISHMANIASIS

Although there is strong evidence that the control and resolution of h uman leishmanial infections depend primarily on activation of parasite -infected macrophages mediated by lymphokines derived from T cells, le ss is known about the nature of the responding cell type(s) which is p rotective or the antigen(s) (Ag[s]) that elicits these cells to respon d. Studies using preparations of whole soluble Ag (''dead Ag'') show t hat patients respond to a wide range of leishmanial Ags. The objective of the present study was to characterize the response of T cells from patients with healing or healed cutaneous or mucosal infections to Ag expressed by or derived from actively infected autologous monocytes ( ''live Ag''). Unfractionated T cells proliferated and produced gamma i nterferon in response to both live and dead Ags. Depletion of CD4(+) T cells resulted in the loss of proliferative and gamma interferon resp onses to both live and dead Ags. The effect of CD8 depletion, although variable and not limited to the cells stimulated by infected monocyte s, was clear for some patients. Expansion of T cells specific for live Ags by using amastigote-infected cells followed by restimulation with fast-protein liquid chromatography-fractionated soluble Ags revealed that a diversity of Ags ore associated with infected monocytes. There may, however, be quantitative differences in the expression of certain Ags since prestimulation with live Ag induced higher responses to res timulation in mucocutaneous leishmaniasis patients than in localized c utaneous leishmaniasis patients. Prestimulation with dead Ag induced s imilar secondary responses in both patient groups.