Keratinocytes produce a lymphocyte inhibitory factor which is partially reversible by an antibody to transforming growth factor-beta.
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.
Nickoloff
B J
BJ
Department of Pathology, University of Michigan, Ann Arbor 48109-0602.
D000906:Antibodies / Q000276:immunology* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D006801:Humans; D007633:Keratins; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000166:cytology*; D015291:Transforming Growth Factors / Q000276:immunology*
D000906:Antibodies; D003470:Culture Media; D007633:Keratins; D015291:Transforming Growth Factors