Fisk B, Flytzanis C N, Pollack M S, Wharton J T, Ioannides C G
Department of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, Houston.
Scand J Immunol. 1994 Dec;40(6):591-600. doi: 10.1111/j.1365-3083.1994.tb03510.x.
T cells from tumour infiltrating lymphocytes (TIL) cultured in media containing IL-2 were shown to mediate in vitro and in vivo antitumor responses. To characterize the T-cell antigen receptor (TCR) V beta expression in autologous cytotoxic effectors we isolated CD3+ CD8+ CD4- cells from cultures of TIL and tumour-associated lymphocytes (TAL) and analysed the TCR V beta repertoire of CD3+ CD8+ CD4- lines of known HLA-A, -B and -C phenotype, using polymerase chain reaction (PCR). These lines showed preferential lysis of autologous tumours and lysed, to a much lesser extent, NK and LAK cell-sensitive targets. Tumour lysis was inhibited by antibodies to CD3 and MHC class I antigens indicating that they are cytotoxic T lymphocytes (CTL). These CD8+ CTL lines expressed a broad distribution of TCR V beta repertoire which was dominated by particular groups of V beta families in each CTL line. However, no predominant expression of one or the same V beta segment in all CTL lines was observed although statistical correlations between V beta family usage and magnitude of the antitumour cytolytic response were found. These results suggest that certain TCR V beta families may be selected by antigen in ovarian tumour-reactive T cells and this selection may be affected by Ag expression, and/or host factors. To our knowledge, this is the first documentation of TCR V beta repertoire of human ovarian tumour-reactive CD3+ CD8+ CD4- CTL from different individuals of known HLA types.
在含有白细胞介素-2的培养基中培养的肿瘤浸润淋巴细胞（TIL）来源的T细胞，已被证明能介导体外和体内抗肿瘤反应。为了表征自体细胞毒性效应细胞中的T细胞抗原受体（TCR）Vβ表达，我们从TIL和肿瘤相关淋巴细胞（TAL）培养物中分离出CD3+ CD8+ CD4-细胞，并使用聚合酶链反应（PCR）分析已知HLA - A、-B和-C表型的CD3+ CD8+ CD4-细胞系的TCR Vβ库。这些细胞系表现出对自体肿瘤的优先裂解作用，对NK和LAK细胞敏感靶标的裂解作用则小得多。肿瘤裂解受到抗CD3和MHC I类抗原抗体的抑制，表明它们是细胞毒性T淋巴细胞（CTL）。这些CD8+ CTL细胞系表达的TCR Vβ库分布广泛，每个CTL细胞系中特定的Vβ家族占主导。然而，尽管发现Vβ家族使用情况与抗肿瘤细胞溶解反应强度之间存在统计相关性，但在所有CTL细胞系中未观察到一个或相同Vβ片段的优势表达。这些结果表明，某些TCR Vβ家族可能在卵巢肿瘤反应性T细胞中被抗原选择，这种选择可能受抗原表达和/或宿主因素影响。据我们所知，这是首次对来自已知HLA类型的不同个体的人卵巢肿瘤反应性CD3+ CD8+ CD4- CTL的TCR Vβ库进行记录。
