title: The magnitude of CD4(+) T-cell activation rather than TCR diversity determines the outcome of Leishmania infection in mice.
abstract: CD4(+) T cells play a critical role in determining the disease outcome in murine cutaneous leishmaniasis, and selective usage of T-cell receptor (TCR) is implied in promoting Leishmania major infection. However, little information is available on TCR usage in Leishmania-specific, IFN-γ-producing CD4(+) T cells. In this study, we investigated the TCR diversity and activation of CD4(+) T cells in a nonhealing model associated with L. amazonensis (La) infection and a self-healing model associated with L. braziliensis (Lb) infection. While marked expansion in the absolute number of several subsets was observed in Lb-infected mice, the percentages of TCR Vβ(+) CD4(+) -cell subsets were comparable in draining LN- and lesion-derived T cells in two infection models. We found that multiple TCR Vβ CD4(+) T cells contributed collectively and comparably to IFN-γ production and that the overall levels of IFN-γ production positively correlated with the control of Lb infection. Moreover, pre-infection with Lb parasites provided cross-protection against secondary La infection, owing to an enhanced magnitude of T-cell activation and IFN-γ production. Collectively, this study suggests that the magnitude of CD4(+) T-cell activation, rather than the TCR diversity, is the major determining factor for the outcome of Leishmania infection.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-107, USA.
authors.forename: L
authors.initials: L
authors.lastname: Xin
authors.forename: J L
authors.initials: JL
authors.lastname: Wanderley
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: D A
authors.initials: DA
authors.lastname: Vargas-Inchaustegui
authors.forename: L
authors.initials: L
authors.lastname: Soong
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D056738:Cross Protection; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D007894:Leishmania mexicana / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma