LEISHMANIA MAJOR-PARASITIZED MACROPHAGES AUGMENT TH2-TYPE T-CELL ACTIVATION

We studied the ability of resident peritoneal M phi, parasitized in vi tro with Leishmania major, to present Ag to three Th2-type T cell clon es that are specific for non-leishmanial Ags. Results indicted that L. major-infected M phi enhanced the proliferation and IL-4 secretion of Th2 T cells in response to stimulation with their cognate Ag. Augment ation of Th2 T cell proliferation was seen in Ag-driven responses but not in mitogenic Con A stimulation. Furthermore, live L. major promast igotes and amastigotes, but not killed parasites, augmented the Th2 T cell response. To delineate the augmentative effect of L. major-infect ed M phi for Th2 T cell activation, we analyzed the cytokines produced by infected M phi in the presence or absence of Th2 T cell clones. Th e supernatants contained IL-1 but not IL-6 or IL-10. Interestingly, ad dition of a neutralizing anti-IL 1 alpha mAb to the cultures reduced t he augmentative effect for Th2 proliferation. Moreover, additional exp eriments showed that IL-1 alpha could substitute for L. major and enha nce T cell activation in cultures consisting of Th2 cells, normal M ph i and Ag. Thus, our study shows that L. major-infected M phi present A gs in a manner that augments Th2 T cell proliferation and IL-4 synthes is, and that the phenomenon is at least in part mediated by IL-1 secre ted by the infected M phi. For purposes of comparison, two non-leishma nial Ag specific Th1-type T cell clones were stimulated with L. major- infected M phi. Our data, as already reported by others, showed that i nfected M phi inhibited the response of Th1 T cells to their cognate A g. Taken together, this report shows that leishmanial-infected M phi f avor the activation of Th2 T cells over Th1 cells and that Th1 and Th2 cells require distinct activation signals from M phi.