title: MHC class II restricted innate-like double negative T cells contribute to optimal primary and secondary immunity to Leishmania major.
abstract: Although it is generally believed that CD4(+) T cells play important roles in anti-Leishmania immunity, some studies suggest that they may be dispensable, and that MHC II-restricted CD3(+)CD4(-)CD8(-) (double negative, DN) T cells may be more important in regulating primary anti-Leishmania immunity. In addition, while there are reports of increased numbers of DN T cells in Leishmania-infected patients, dogs and mice, concrete evidence implicating these cells in secondary anti-Leishmania immunity has not yet been documented. Here, we report that DN T cells extensively proliferate and produce effector cytokines (IFN-γ, TNF and IL-17) and granzyme B (GrzB) in the draining lymph nodes and spleens of mice following primary and secondary L. major infections. DN T cells from healed mice display functional characteristics of protective anti-Leishmania memory-like cells: rapid and extensive proliferation and effector cytokines production following L. major challenge in vitro and in vivo. DN T cells express predominantly (> 95%) alpha-beta T cell receptor (αβ TCR), are Leishmania-specific, restricted mostly by MHC class II molecules and display transcriptional profile of innate-like genes. Using in vivo depletion and adoptive transfer studies, we show that DN T cells contribute to optimal primary and secondary anti-Leishmania immunity in mice. These results directly identify DN T cells as important players in effective and protective primary and secondary anti-L. major immunity in experimental cutaneous leishmaniasis.
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Mou
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Ifeoma
authors.initials: I
authors.lastname: Okwor
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Ping
authors.initials: P
authors.lastname: Jia
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Kanami
authors.initials: K
authors.lastname: Orihara
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Jude Ezeh
authors.initials: JE
authors.lastname: Uzonna
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D007124:Immunoenzyme Techniques; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta