Tumor-specific CD4(+) suppressor T-cell clone capable of inhibiting rejection of syngeneic sarcoma in A/J mice.
Elimination of CD4(+) T cells by anti-CD4 antibody caused regression of a methylcholanthrene-induced S713a sarcoma growing in syngeneic A/J mice, and the tumor regression was essentially required for CD8(+) T cells. A CD4(+) T-cell clone, designated T595B1, was established to elucidate the characteristics of CD4(+) suppressor T cells. T595B1 expressed CD3, T-cell receptor (TCR)beta, TCR-Vbeta2, CD4, CD25, CD45RB, CD44, LFA-1, and ICAM-1 molecules on its cell surface and showed MHC class II I-E(k)-restricted tumor antigen-specific proliferation. T595B1 cells specifically suppressed in vitro CTL induction of S713a in a dose-dependent manner. Furthermore, culture supernatant of T595B1 cells also suppressed in vitro CTL induction, but its suppressive activity was not specific. Cytokine analyses revealed that T595B1 cells secreted IL-4, IL-5, IL-6, and IL-10 but not IFN-gamma, IL-2, TNF, or TGFbeta, indicating that this clone belongs to the so-called T helper 2 (Th2) type. However, the suppressive activity of the culture supernatant to the in vitro CTL induction was not abrogated by any neutralizing antibody to IL-4, IL-5, IL-6, IL-10, or TGF-beta. Repeated adoptive transfer of T595B1 cells into syngeneic immune mice entirely impaired their capacity to reject S713a sarcoma, resulting in progressive tumor growth in these mice.
Department of Immunology, Kochi Medical School, Nankoku-shi, Kochi, Japan.
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Fu
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Shen
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Fujimoto
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D008748:Methylcholanthrene; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010641:Phenotype; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D008748:Methylcholanthrene