Autoreactive T-cell clones which suppress cytotoxic T cell responses

• Published in: International immunology Vol. 3; no. 4; p. 377
• Main Authors: Sakatsume, M, Harada, Y, Ling, X, Yasumoto, A, Kurosu, A, Koseki, H, Saito, T, Kantake, M, Taniguchi, M
• Format: Journal Article
• Language: English
• Published: England 01.04.1991
• Subjects: Animals; Antigen-Presenting Cells - immunology; Autoimmunity; CD4 Antigens; Clone Cells - immunology; Cytotoxicity, Immunologic; G(M3) Ganglioside - immunology; Melanoma, Experimental - immunology; Mice; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Regulatory - immunology
• ISSN: 0953-8178
• DOI: 10.1093/intimm/3.4.377

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-Ab/GM3+) B16 melanoma or I-Ab-transfected GM3+ L cells, but not by GM3-/I-Ab mutant melanoma, EL 4, or I-Ad/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.