Specificities and functions of CD4+ HLA class II-restricted T cell clones against a human sarcoma: evidence for several recognized antigens.
CD4+ T cells play an important role for tumor immunity in animal tumor models, yet there are few reports about the role of CD4+ HLA class II-restricted T cells in the immune response against human tumors. Against a human sarcoma exclusively CD4+, T cell clones could be established. These T cell clones were cytotoxic and secreted TNF and additional cytokines in response to the IFN-gamma-treated, HLA class II-positive autologous sarcoma cells. Several Ags were recognized by representative T cell clones: an Ag presented by HLA-DR and specific for the sarcoma; Ags presented by both HLA-DR alleles of the sarcoma, HLA-DR4 and -15, and shared by allogenic HLA-DR matched cell lines of different tissue lineages, including B cell blasts; and a sarcoma Ag presented by HLA-DP or DQ. Cytokine profiles of sarcoma-reactive T cell clones were dependent on the cytokine environment present during establishment of the T cell clones. The addition of exogenous IL-4 shifted the cytokine patterns of sarcoma-reactive T cell clones from Th1-like patterns to Th0/Th2-like patterns and decreased IL-10 production. TNF, IFN-gamma, IL-4, and supernatants of T cell clones induced HLA-DR expression on the sarcoma cells and, thus, were able to enhance Ag presentation. This autologous T cell response to a human sarcoma represents a new model for HLA class II-restricted T cell responses to human tumors.
Heike
M
M
First Department of Medicine, University of Mainz, Germany.
Schlaak
J
J
Schulze-Bergkamen
H
H
Heyl
S
S
Herr
W
W
Schmitt
U
U
Schneider
P M
PM
Meyer zum Büschenfelde
K H
KH
D000008:Abdominal Neoplasms / Q000235:genetics / Q000276:immunology*; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002999:Clone Cells; D016207:Cytokines / Q000378:metabolism / Q000502:physiology; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000235:genetics / Q000502:physiology*; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D008297:Male; D012509:Sarcoma / Q000235:genetics / Q000276:immunology*; D014407:Tumor Cells, Cultured
D016207:Cytokines; D000939:Epitopes; D006684:HLA-DR Antigens; D007371:Interferon-gamma