Autoreactive T-cell clones which suppress cytotoxic T cell responses.
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.
Sakatsume
M
M
Division of Molecular Immunology, School of Medicine, Chiba University, Japan.
Harada
Y
Y
Ling
X
X
Yasumoto
A
A
Kurosu
A
A
Koseki
H
H
Saito
T
T
Kantake
M
M
Taniguchi
M
M
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015551:Autoimmunity; D015704:CD4 Antigens; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005679:G(M3) Ganglioside / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D015704:CD4 Antigens; D005679:G(M3) Ganglioside