The Journal of Immunology, Vol 159, Issue 4 1828-1834, Copyright © 1997 by American Association of Immunologists

ARTICLES

Presentation via the class I pathway by Leishmania amazonensis-infected macrophages of an endogenous leishmanial antigen to CD8+ T cells

PE Kima, NH Ruddle and D McMahon-Pratt
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA.

CD8+ T cells play a protective role in immunity to cutaneous leishmaniasis. However, it has been unclear how these cells execute this function, since results from several investigations attempting to demonstrate recognition of Leishmania-infected macrophages by CD8+ T cells have been contradictory. In this study, we report the generation of CD8+ T cell lines specific for GP46/M-2, a leishmanial Ag, previously shown to protectively immunize mice against a Leishmania amazonensis challenge. Using T cell cytolysis and IFN-gamma production to assess CD8+ T cell activation, we show that in addition to recognizing mammalian cells transfected with GP46/M-2, these CD8+ T cell lines also recognize macrophages infected with Leishmania amazonensis. MHC class I presentation of GP46/M-2 by infected macrophages can be blocked by treatment with brefeldin A and also by inhibitors of the cytosolic multicatalytic proteasome, N-acetyl-L- leucinyl-L-leucinal-L-norleucinal and N-acetyl-L-leucinyl-L- leucinylmethional. These results suggest that this leishmanial Ag is processed in the macrophage cytoplasm and is presented to CD8+ T cells via the classical pathway of MHC class I presentation. The relevance of these findings as they impact on our understanding of the biology of the parasite within the macrophage is discussed.

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