Normal Human Keratinocytes Inhibit the Proliferation of Unprimed T Cells by TGFβ and PGE2, but Not IL-10

Abstract

Recent investigations in antigen processing suggest that many hematopoietic and nonhematopoietic cell types are capable of presenting alloantigen to T lymphocytes. However, the role of certain nonclassical antigen presenting cells is blurred by their apparent ability to down-regulate the immune response as well as activate immune cells, depending upon the microenvironment and the functional state of the responding cells. In this study we examine the ability of cultured allogeneic keratinocytes to inhibit the response of naive T cells to alloantigen or to anti-CD3. Our results demonstrate that as few as 6.25 × 103keratinocytes significantly inhibited T cell proliferation in response to alloantigen as well as anti-CD3-mediated stimulation (49 and 54%, respectively). HK-mediated inhibition of T cell proliferation did not require cell contact, suggesting that inhibition is mediated by cytokines or other soluble factors. This was further supported by experiments demonstrating the inducibility of HK inhibitory activity in the presence of FCS, and the partial blockage of HK inhibitory activity through the addition of indomethacin or anti-TGFβ antibody. Interestingly, the data suggest that IL-10, a known immunomodulatory cytokine, does not play a role in the inhibitory activity seen in this system. Taken together the results suggest that HK have the potential to regulate the response of T cells to antigen presented by other APC through the production of soluble factors.