AUTOREACTIVE T-CELL CLONES WHICH SUPPRESS CYTOTOXIC T-CELL RESPONSES

作者：SAKATSUME M; HARADA Y; LING X; YASUMOTO A; KUROSU A; KOSEKI H; SAITO T; KANTAKE M; TANIGUCHI M

来源：International Immunology, 1991, 3(4): 377-384.

DOI：10.1093/intimm/3.4.377

• AUTOREACTIVE T-CELL CLONE
• SUPPRESSOR T-CELL
• CTL
• GM3
• CLASS-II+ MELANOMA

Autoreactive T-cell clones (Thy 1+, CD4+, CD3+) which suppress generation of cytotoxic T lymphocytes (CTL) were established in long-term in vitro culture by stimulation with GM3-liposomes or soluble melanoma (B16) antigen composed of GM3. The T-cell receptors (TCR) of two representative clones analyzed used the same TCR-alpha- and V13+ beta-chains. The clones produce only interferon-gamma(IFN-gamma) but not interleukins (IL)2 and 4, despite their CD4+ phenotype, suggesting that they are not a typical TH1 or TH2 type. The clones are effectively stimulated by IFN-gamma treated (I-A(b)/GM3+) B16 melanoma or I-A(b)-transfected GM3+ L cells, but not by GM3-/I-A(b) mutant melnaoma, EL 4, or I-A(d/k)-transfected L cells. This strongly suggested the involvement of GM3/class II in T-cell recognition. Antigen specificity was required for stimulation of the clones. However, once stimulated, they suppressed CTL generation in an antigen non-specific fashion. As class II+ B16 melanoma cells effectively function as antigen-presenting cells to stimulate the autoreactive suppressor T cell (Ts) clones of this type, this negative circuit between class II+ tumor cells and IFN-gamma-producing Ts would be a possible mechanism whereby tumor cells could escape the immune system.

• 出版日期1991-4