title: Leishmania infantum-specific T cell lines derived from asymptomatic dogs that lyse infected macrophages in a major histocompatibility complex-restricted manner.
abstract: Protective immunity to leishmaniasis has been demonstrated in murine models to be mediated by T cells and the cytokines they produce. We have previously shown that resistance to experimental Leishmania infantum infection in the dog, a natural host and reservoir of the parasite, is associated with the proliferation of peripheral blood mononuclear cells (PBMC) to parasite antigen and to the production of interleukin-2 and tumour necrosis factor. In this study we show that PBMC from asymptomatic experimentally infected dogs produce interferon-gamma upon parasite antigen-specific stimulation, whereas lymphocytes from symptomatic dogs do not. In addition, we report for the first time the lysis of L. infantum-infected macrophages by PBMC from asymptomatic dogs and by parasite-specific T cell lines derived from these animals. These T cell lines were generated by restimulation in vitro with parasite soluble antigen and irradiated autologous PBMC as antigen-presenting cells. We show that lysis of infected macrophages by T cell lines is major histocompatibility complex restricted. Characterization of parasite-specific cytotoxic T cell lines revealed that the responding cells are CD8+. However, for some animals, CD4+ T cells that lyse infected macrophages were also found. In contrast to asymptomatic dogs, lymphocytes from symptomatic dogs failed to proliferate and produce interferon-gamma after Leishmania antigen stimulation in vitro and were not capable of lysing infected macrophages. These results suggest that both the production of interferon-gamma and the destruction of the parasitized host cells by Leishmania-specific T cells play an important role in resistance to visceral leishmaniasis.
authors.affiliation: Department of Immunology, Faculty of Veterinary Medicine, University of Utrecht, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Pinelli
authors.forename: R M
authors.initials: RM
authors.lastname: Gonzalo
authors.forename: C J
authors.initials: CJ
authors.lastname: Boog
authors.forename: V P
authors.initials: VP
authors.lastname: Rutten
authors.forename: D
authors.initials: D
authors.lastname: Gebhard
authors.forename: G
authors.initials: G
authors.lastname: del Real
authors.forename: E J
authors.initials: EJ
authors.lastname: Ruitenberg
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004285:Dogs; D006649:Histocompatibility Antigens / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D018314:Leishmania infantum / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D006649:Histocompatibility Antigens; D007371:Interferon-gamma