title: Differential kinetics of antigen-specific CD4+ and CD8+ T cell responses in the regression of retrovirus-induced sarcomas.
abstract: Despite the accepted role for CD4+ T cells in immune control, little is known about the development of Ag-specific CD4+ T cell immunity upon primary infection. Here we use MHC class II tetramer technology to directly visualize the Ag-specific CD4+ T cell response upon infection of mice with Moloney murine sarcoma and leukemia virus complex (MoMSV). Significant numbers of Ag-specific CD4+ T cells are detected both in lymphoid organs and in retrovirus-induced lesions early during infection, and they express the 1B11-reactive activation-induced isoform of CD43 that was recently shown to define effector CD8+ T cell populations. Comparison of the kinetics of the MoMSV-specific CD4+ and CD8+ T cell responses reveals a pronounced shift toward CD8+ T cell immunity at the site of MoMSV infection during progression of the immune response. Consistent with an important early role of Ag-specific CD4+ T cell immunity during MoMSV infection, CD4+ T cells contribute to the generation of virus-specific CD8+ T cell immunity within the lymphoid organs and are required to promote an inflammatory environment within the virus-infected tissue.
authors.affiliation: Department of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Koen
authors.initials: K
authors.lastname: Schepers
authors.forename: Mireille
authors.initials: M
authors.lastname: Toebes
authors.forename: Gitte
authors.initials: G
authors.lastname: Sotthewes
authors.forename: Florry A
authors.initials: FA
authors.lastname: Vyth-Dreese
authors.forename: Trees A M
authors.initials: TA
authors.lastname: Dellemijn
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
authors.forename: Ferry
authors.initials: F
authors.lastname: Ossendorp
authors.forename: Ton N M
authors.initials: TN
authors.lastname: Schumacher
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000096:biosynthesis; D007111:Immunity, Cellular; D016130:Immunophenotyping; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000276:immunology; D008980:Moloney murine sarcoma virus / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D012075:Remission, Spontaneous; D012513:Sarcoma, Experimental / Q000276:immunology*; D014412:Tumor Virus Infections / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments