title: CD98 Heavy Chain Is a Potent Positive Regulator of CD4+ T Cell Proliferation and Interferon-γ Production In Vivo.
abstract: Upon their recognition of antigens presented by the MHC, T cell proliferation is vital for clonal expansion and the acquisition of effector functions, which are essential for mounting adaptive immune responses. The CD98 heavy chain (CD98hc, Slc3a2) plays a crucial role in the proliferation of both CD4+ and CD8+ T cells, although it is unclear if CD98hc directly regulates the T cell effector functions that are not linked with T cell proliferation in vivo. Here, we demonstrate that CD98hc is required for both CD4+ T cell proliferation and Th1 functional differentiation. T cell-specific deletion of CD98hc did not affect T cell development in the thymus. CD98hc-deficient CD4+ T cells proliferated in vivo more slowly as compared with control T cells. C57BL/6 mice lacking CD98hc in their CD4+ T cells could not control Leishmania major infections due to lowered IFN-γ production, even with massive CD4+ T cell proliferation. CD98hc-deficient CD4+ T cells exhibited lower IFN-γ production compared with wild-type T cells, even when comparing IFN-γ expression in cells that underwent the same number of cell divisions. Therefore, these data indicate that CD98hc is required for CD4+ T cell expansion and functional Th1 differentiation in vivo, and suggest that CD98hc might be a good target for treating Th1-mediated immune disorders.
authors.affiliation: Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kurihara
authors.affiliation: Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Arimochi
authors.affiliation: Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan.
authors.forename: Zaied Ahmed
authors.initials: ZA
authors.lastname: Bhuyan
authors.affiliation: Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan.
authors.forename: Chieko
authors.initials: C
authors.lastname: Ishifune
authors.affiliation: Division of Laboratory Animal Resources, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Tsumura
authors.affiliation: Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Aichi, Japan.
authors.forename: Morihiro
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Aichi, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kitamura
authors.affiliation: Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Maekawa
authors.affiliation: Department of Immunology and Parasitology, Graduate School of Medicine, Tokushima University, Tokushima, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yasutomo
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation / Q000502:physiology*; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018417:Th1 Cells / Q000276:immunology
chemical_list: D027282:Fusion Regulatory Protein 1, Heavy Chain; D007371:Interferon-gamma