Minor histocompatibility antigens, defined by graft-vs.-host disease-derived cytotoxic T lymphocytes, show variable expression on human skin cells

Publisher Website
Google Scholar
Abstract
Little is known on the effector mechanisms inducing the cutaneous lesions observed during acute graft‐vs.‐host disease (aGvHD) after allogeneic bone marrow transplantation (BMT). Histological findings have indicated that infiltrating CD8+ lymphocytes probably play a role. We addressed the question of whether host minor histocompatibility (mH) antigen‐reactive cytotoxic T lymphocytes (CTL) could account for this phenomenon via direct lysis of the epidermal cell layer. Six CTL clones, obtained from peripheral blood lymphocytes of patients suffering from aGvHD, each recognizing a well‐characterized MHC class I‐restricted mH antigen epitope, were tested on cultured keratinocytes of nine MHC and mH antigen‐typed donors. Four of six mH antigen‐specific CTL clones lysed unstimulated MHC class I‐expressing, as well as recombinant interferon‐γ (rlFN‐γ)‐activated, ICAM‐1, MHC class I‐ and II‐expressing keratinocytes. Two strongly cytolytic CTL clones showed no recognition of keratinocytes of donors whose phytohemagglutinin‐activated T cell lines were readily lysed. With respect to aGvHD, the results imply that some class I‐restricted CTL obtained from peripheral blood lymphocytes of aGvHD patients have the in vitro potential to destroy resting as well as IFN‐γ‐activated epidermal cells, whereas others do not. In other words, CTL‐defined human mH antigens vary with respect to their expression in the skin. It is intriguing that those minor H antigens which cannot be detected on human keratinocytes in vitro are those known to be associated with the occurrence of GvHD.