Antigen presentation by human dermal fibroblasts: activation of resting T lymphocytes.
We have shown that human dermal fibroblasts, exposed to interferon-gamma (IFN-gamma) to induce surface class II major histocompatibility complex (MHC) antigens, were capable of presenting tetanus toxoid (TT) antigen to human TT-specific T cell clones. Antigen presentation by fibroblasts was antigen dependent, required HLA-DR expression by fibroblasts, and was MHC restricted. In contrast, we now report that IFN-gamma-treated fibroblasts are unable to present TT antigen to purified resting T cells obtained from the peripheral blood of TT-immune donors. In addition, although IFN-gamma-treated fibroblasts were able to stimulate alloreactive T cell clones, they were unable by themselves to stimulate primary allogeneic responses in resting T cells. The failure of fibroblasts to stimulate resting T cells was not due to suppressor effects by fibroblasts, because induction of TT and alloantigen responses in resting T cells by monocytes was not inhibited by the presence of fibroblasts. On the contrary, IFN-treated fibroblasts were synergistic with small numbers of monocytes in activating resting T cells. In addition, the failure of antigen presentation by fibroblasts to resting T cells was reversed by the addition of recombinant human interleukin 2 (rIL 2) to cultures, but not of purified human interleukin 1 (IL 1). These results emphasize that the requirements for activation of resting T cells differ from those of T cell clones. Although fibroblasts can efficiently present antigen to T cell clones, antigen presentation by fibroblasts to resting T cells requires the addition of exogenous IL 2. It is postulated that fibroblasts differ from classical antigen-presenting cells in that fibroblasts are incapable of stimulating the production of IL 2 in resting T cells.
D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002450:Cell Communication; D002999:Clone Cells / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology* / Q000502:physiology; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology; D007399:Interphase; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology / Q000502:physiology; D012867:Skin / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology
D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D007376:Interleukin-2; D013745:Tetanus Toxoid