Cytokine production by CD4+ T-cells responding to antigen presentation by melanoma cells.
Melanoma cells are unusual because, unlike most epithelial tumours, constitutive expression of HLA class II antigens is common. We have previously demonstrated that a peptide-specific CD4+ T-cell clone proliferates briskly in response to peptide and HLA class II expressing melanoma cell lines derived from metastases. Here we demonstrate that these CD4+ T-cells secrete large amounts of interferon-gamma (IFNgamma) and interleukin-10 (IL10), and insignificant quantities of IL2 or IL4, in response to peptide presentation by both melanoma and autologous B-cells. T-cells produced more IL10 when responding to peptide presentation by melanoma cells compared with B-cells, and less IFNgamma (P<0.01). Addition of IL12 did not alter the cytokines produced but increased the T-cell production of both, especially the production of IL10 in response to peptide presentation by melanoma cells. Our data suggest that differential cytokine production by CD4+ T-cells in response to peptide presentation by HLA class II expressing tumour cells may contribute to tolerance to tumour antigens.
Brady
M S
MS
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. bradym@mskcc.org
Eckels
D D
DD
Lee
F
F
Ree
S Y
SY
Lee
J S
JS
D000938:Antigen-Presenting Cells / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008545:Melanoma / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D016207:Cytokines; D007376:Interleukin-2; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma