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.
Fu
T
T
Department of Immunology, Kochi Medical School, Nankoku-shi, Kochi, Japan.
Shen
Y
Y
Fujimoto
S
S
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