Presentation via the class I pathway by Leishmania amazonensis-infected macrophages of an endogenous leishmanial antigen to CD8+ T cells.
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.
Kima
P E
PE
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA.
Ruddle
N H
NH
McMahon-Pratt
D
D
D000818:Animals; D017951:Antigen Presentation; D000953:Antigens, Protozoan / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D007891:Leishmania / Q000276:immunology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008808:Mice, Inbred CBA
D000953:Antigens, Protozoan; D016207:Cytokines; D015395:Histocompatibility Antigens Class I