Co-stimulation with IL-2, but not via CD28, overcomes immunosuppression by breast tumour-derived factors on the in vitro stimulation of human T-cells.
In order to investigate the mode of action of tumour-derived immunosuppressive factor from breast cancer (TDS) we examined its function on human T-cells stimulated via CD3 and co-stimulated via CD28 or the IL-2 receptor. When added at the initiation of culture, TDS inhibited anti-CD3 stimulation and co-stimulation by anti-CD28. In contrast, co-stimulation with IL-2 greatly diminished the TDS inhibition of anti-CD3 stimulated cells. Activation by IL-2 alone was also inhibited at the initiation of culture. When PBMC were activated with IL-2 or anti-CD3 for three days and then exposed to TDS for a further 3 days, only the proliferation of the cells pre-activated with IL-2 was inhibited; the cells pre-activated via CD3 were refractory to TDS inhibition. Pre-activation with anti-CD3 for 48 h was required for this to develop. The cytotoxicity of cells pre-activated with anti-CD3 was lower than that of cells exposed to IL-2, but killing obtained from cultures pre-activated with anti-CD3 plus IL-2 was equivalent to that obtained with IL-2 alone and additionally, these pre-activated cells were not subject to inhibition upon subsequent exposure to TDS.
Xie
J
J
University of Glasgow Department of Surgery, Glasgow Royal Infirmary, UK.
Gallagher
G
G
D001943:Breast Neoplasms / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000494:pharmacology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007376:Interleukin-2 / Q000494:pharmacology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D018106:CD28 Antigens; D017252:CD3 Complex; D007376:Interleukin-2