title: Preferentially expanding Vγ1+γδ T cells are associated with protective immunity against Plasmodium infection in mice.
abstract: γδ T cells play a crucial role in controlling malaria parasites. Dendritic cell (DC) activation via CD40 ligand (CD40L)-CD40 signaling by γδ T cells induces protective immunity against the blood-stage Plasmodium berghei XAT (PbXAT) parasites in mice. However, it is unknown which γδ T-cell subset has an effector role and is required to control the Plasmodium infection. Here, using antibodies to deplete TCR Vγ1+cells, we saw that Vγ1+γδ T cells were important for the control of PbXAT infection. Splenic Vγ1+γδ T cells preferentially expand and express CD40L, and both Vγ1+and Vγ4+γδ T cells produce IFN-γ during infection. Although expression of CD40L on Vγ1+γδ T cells is maintained during infection, the IFN-γ positivity of Vγ1+γδ T cells is reduced in late-phase infection due to γδ T-cell dysfunction. In Plasmodium-infected IFN-γ signaling-deficient mice, DC activation is reduced, resulting in the suppression of γδ T-cell dysfunction and the dampening of γδ T-cell expansion in the late phase of infection. Our data suggest that Vγ1+γδ T cells represent a major subset responding to PbXAT infection and that the Vγ1+γδ T-cell response is dependent on IFN-γ-activated DCs.
authors.affiliation: Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Inoue
authors.affiliation: Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Niikura
authors.affiliation: Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Asahi
authors.affiliation: Research Institute for Biological Sciences, Tokyo University of Science, Chiba, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.affiliation: Laboratory of Parasitology, School of Life and Environmental Science, Azabu University, Kanagawa, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawakami
authors.affiliation: Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan.
authors.forename: Fumie
authors.initials: F
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D008288:Malaria / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010962:Plasmodium berghei / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D019013:CD40 Antigens; D016692:Receptors, Antigen, T-Cell, gamma-delta; D023201:CD40 Ligand; D007371:Interferon-gamma
keywords: CD40L; Dendritic cells; IFN-γ; Malaria; Vγ1+ γδ T cells; γδ T cells; γδ T-cell exhaustion