呼吸器・消化器領域のへん平上皮癌 細胞分子レベルからの解析 Ｔ‐ｃｅｌｌレベルから―頭頚部へん平上皮癌を認識する細胞障害性Ｔ細胞について

Abstract

Human cytotoxic T-lymphocyte (CTL) lines with specificity restricted for autologous squamous cell carcinoma of the head and neck (SCCHN) were established from peripheral blood lymphocytes (PBL) obtained from a patient with cancer of the tongue. The CTL lines were CD3+CD8+CD11b-HLA-DR+T cell receptors (TCR) α /β+. They were tested in 4 h 51Cr-release assays against SCCHN cell lines (n=11) and a variety of non-squamous human tumors (n=9) and normal (n=5) cell targets. They were found to lyse only autologous rumor (AuTu, PCI-50) and seven allogeneic SCCHN cell lines. Of these tumor cell lines, three cell lines shared a HLA-A2 locus with the AuTu, while the other two lines shared HLA-B44 with AuTu. Lysis of AuTu and the allogeneic SCCHN targets of the established CTL lines appeared to be MHC-class I restricted. The CTL lines proliferated in vitro in response to autologous PCI-50 or an allogeneic SCCHN cell line. Analysis of the TCRβ chain genes for the CTL and CTL clones indicated that two different CTL populations (Vβ6 and Vβ2) are able to recognize SCCHN-associated antigen (s) and that Vβ6 T cells are HLA-A2-restricted, while Vβ2 T cells may be HLA-B44-restricted.While the growth of PCI-50 cells in culture was significantly inhibited by the supernatants of A-NK cells, those of the CTL line were not growth inhibitory. On the other hand, the lysis of AuTu targets by the CTL line was increased by preincubation of tumor cells with TNFα or IFNγ. These cytokines augmented the expression of HLA-class I, HLA-class II and intercellular adhesion molecule I (ICAM-I) on PCI-50 cells. The CTL incubated in the presence of HLA-A2 SCCHNs but not HLA-A2 gastric carcinoma produced TNFα, IFNγ and GMCSF.