Minor histocompatibility antigens, defined by graft-vs.-host disease-derived cytotoxic T lymphocytes, show variable expression on human skin cells.
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-gamma (rIFN-gamma)-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 a GvHD, the results imply that some class I-restricted CTL obtained from peripheral blood lymphocytes of a GvHD patients have the in vitro potential to destroy resting as well as IFN-gamma-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.
Department of Immunohaematology, University Hospital, Leiden, The Netherlands.
M
M
De Bueger
A
A
Bakker
J J
JJ
Van Rood
E
E
Goulmy
D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000032:analysis; D002478:Cells, Cultured; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology; D015603:Keratinocytes / Q000276:immunology; D015778:Minor Histocompatibility Antigens / Q000276:immunology*; D011994:Recombinant Proteins; D012867:Skin / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I; D015778:Minor Histocompatibility Antigens; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma