Autologous melanoma-induced activation of regulatory T cells that suppress cytotoxic response.
The host immune response toward autologous human cancer is subject to regulation by the immunoregulatory network. We show that certain CD4+ T cell clones, derived from melanoma involved lymph node lymphocytes and from PBL stimulated by autologous melanoma cells, selectively down-regulated the induction of cytotoxic immune response of PBL against the respective autologous melanoma cells in two autologous systems. In both systems, only the generation of cytotoxic response against the autologous melanoma cells were suppressed. Cytotoxic response against EBV-infected autologous lymphoblastoid cell line in one case and cytotoxic responses against allogeneic targets in the other were not affected. In addition to suppressor activity selectively expressed against the autologous melanoma cells, the T cell clones up-regulated their Tac receptors when cocultured with the autologous melanoma cells and APC. These results support the existence of a putative tumor Ag-driven activation of regulatory T cells that affect cytotoxic immune response, in vitro, against autologous human melanoma.
Chakraborty
N G
NG
Department of Medicine, University of Connecticut School of Medicine, Farmington 06032.
Twardzik
D R
DR
Sivanandham
M
M
Ergin
M T
MT
Hellstrom
K E
KE
Mukherji
B
B
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002470:Cell Survival; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007108:Immune Tolerance; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000502:physiology; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D015291:Transforming Growth Factors / Q000502:physiology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D015854:Up-Regulation
D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D015291:Transforming Growth Factors; D007371:Interferon-gamma