Filgueira L, Zuber M, Merlo A, Harder F, Heberer M, Spagnoli G C
Department of Surgery, University of Basel, Switzerland.
Eur J Cancer. 1993;29A(12):1754-60. doi: 10.1016/0959-8049(93)90119-z.
Therapeutic effects of tumour infiltrating lymphocytes (TIL) rely on T-cell receptor (TCR) engagement. In this work, the expression of five TCR alpha/beta variable (V) domains was quantitatively analysed by means of a panel of monoclonal antibodies (Mab) recognising gene products from TCR V alpha 2, V beta 5, V beta 6, V beta 8 and V beta 12 families in freshly isolated TIL and in autologous peripheral blood mononuclear cells (PBMC) from patients with neoplasms. In 3 out of 6 cases, differences in the expression of V beta 5, V beta 6, V beta 8 or V beta 12 could be detected. TIL populations were expanded by using recombinant human interleukin-2 (rhIL-2) alone or in addition to solid phase bound anti-CD3 Mab. Cultured TIL showed similar CD4/CD8 ratios and cytotoxic activity against autologous neoplastic target cells, regardless of the activation protocol. In 4 patients, the expression of TCR alpha/beta V gene products, as compared with TIL from freshly excised tumours, was found to be modified in cultured TIL, especially in cell populations activated with rhIL-2 only. These results indicate that TCR V gene usage in TIL may quantitatively differ from that in PBMC. TIL culture protocols using rhIL-2 alone or in combination with solid phase bound anti-CD3 may result in differential expression of discrete TCR V families.
肿瘤浸润淋巴细胞（TIL）的治疗效果依赖于T细胞受体（TCR）的结合。在本研究中，通过一组单克隆抗体（Mab）对5种TCRα/β可变（V）结构域的表达进行了定量分析，这些单克隆抗体可识别来自TCR Vα2、Vβ5、Vβ6、Vβ8和Vβ12家族的基因产物，分析对象为新鲜分离的TIL以及肿瘤患者的自体外周血单个核细胞（PBMC）。在6例中的3例中，可检测到Vβ5、Vβ6、Vβ8或Vβ12表达的差异。单独使用重组人白细胞介素-2（rhIL-2）或除固相结合抗CD3 Mab之外还使用rhIL-2来扩增TIL群体。无论激活方案如何，培养的TIL均显示出相似的CD4/CD8比率以及对自体肿瘤靶细胞的细胞毒性活性。在4例患者中，发现与新鲜切除肿瘤的TIL相比，培养的TIL中TCRα/β V基因产物的表达发生了改变，尤其是仅用rhIL-2激活的细胞群体。这些结果表明，TIL中TCR V基因的使用在数量上可能与PBMC中的不同。单独使用rhIL-2或与固相结合抗CD3联合使用的TIL培养方案可能导致离散的TCR V家族的差异表达。
