Differential kinetics of antigen-specific CD4+ and CD8+ T cell responses in the regression of retrovirus-induced sarcomas.
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.
Schepers
Koen
K
Department of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Toebes
Mireille
M
Sotthewes
Gitte
G
Vyth-Dreese
Florry A
FA
Dellemijn
Trees A M
TA
Melief
Cornelis J M
CJ
Ossendorp
Ferry
F
Schumacher
Ton N M
TN
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*
D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments