Keratinocytes produce a lymphocyte inhibitory factor which is partially reversible by an antibody to transforming...

The active participation by keratinocytes (KCs) during cutaneous inflammation involves production of various immunologically active molecules. While interleukin-1 (IL-1) is a well-known KC-derived activator of lymphocytes, less attention has been directed towards characterization of non-PGE KC-derived lymphocyte inhibitory factors. To determine whether transforming growth factor-beta (TGF-beta), which has recently been found to be produced by KCs, may be a biologically important constituent of KC-conditioned medium, we measured the ability of neutralizing antibody of TGF-beta to reverse the inhibitory effect of KC-conditioned medium on mixed lymphocyte reactions (MLR). Not only did exogenously added TGF-beta inhibit the MLR, but KC-conditioned media also inhibited the MLR, and this inhibition was partially reversed using the neutralizing antibody as detected by 3H-thymidine incorporation and phase contrast microscopy. Thus, KC-derived TGF-beta may serve as an important inhibitor of lymphocyte proliferation. These results suggest that the balance of cutaneous immunohomeostasis may involve several different KC-derived factors which may be either lymphocyte activating such as IL-1, or lymphocyte inhibitory such as PGE2 and TGF-beta.