Recognition of keratinocytes by cytotoxic T cells specific for conventional HLA class-I alloantigen.
This study analyzed whether human keratinocytes (KC) express conventional HLA class-I molecules as detected by class-I-specific cytotoxic T lymphocytes (CTL), and whether exposure of KC to interferon-gamma (IFN-g) is required for CTL recognition. Basal KC grown in serum-free medium and exposed to recombinant IFN-g for 24-96 h were used as targets in 51Cr-release assays. Target-cell susceptibilities to lysis were compared by analyzing the lytic unit (LU) activity of a given CTL population against IFN-g-treated and untreated KC. CTL effectors were cloned from alloantigen-primed cultures by limiting dilution in the presence of antigenic B lymphoblastoid cells (BCLL) and IL-2. These T-cell clones lysed appropriate BCLL and PHA blasts but not third-party BCLL or K562. Lysis of antigenic BCLL was specifically blocked by antibodies against CD3 or class-I antigens. Specificity of the clones for conventional class-I antigen was demonstrated by cytotoxicity tests employing a panel of HLA-typed BCLL. The clones specifically lysed KC syngeneic with the original effector immunogen, and lysis was also blocked by anti-class-I antibodies. The effect of IFN-g treatment was to increase KC susceptibility to lysis by these clones. From 3-25 times more LU were measured against IFN-g-treated KC than against nontreated KC, and the degree of enhancement was similar for KC treated with concentrations of IFN-g ranging from 2.5-200 U/ml. This effect of IFN-g treatment on KC lysis by CTL, which was detected after only 24 h at all doses tested, emphasizes the potential role of IFN-g in enhancing CTL-mediated antiviral epidermal immunity and in exacerbating epidermal disease mediated by specific lytic T cells. In addition, the finding that normal human KC can be recognized by MHC class-I-specific CTL demonstrates that KC do express conventional class-I-antigens and that KC lysis by CTL can occur independently of exogenous cytokines.
Symington
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FW
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Santos
E B
EB
D000328:Adult; D001402:B-Lymphocytes; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007519:Isoantigens / Q000276:immunology*; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D007519:Isoantigens; D011994:Recombinant Proteins; D007371:Interferon-gamma