Ferrini S, Cambiaggi A, Meazza R, Sforzini S, Marciano S, Mingari M C, Moretta L
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Eur J Immunol. 1994 Oct;24(10):2294-8. doi: 10.1002/eji.1830241005.
A new anti-p58 monoclonal antibody (mAb), termed CH-L, has been used to characterize a minor subset of T lymphocytes co-expressing p58 and CD3 molecules. In two-color immunofluorescence analysis, CH-L+CD3+ cells represented 0.5 to 6% of the peripheral blood lymphocytes (in 20 healthy donors). Clonal analysis showed that most CD3+CH-L+ T cell clones expressed the CD8+4- T cell receptor (TcR) alpha/beta+ phenotype, while only a few were CD8-4+ TcR alpha/beta, CD8-4- TcR alpha/beta+ or CD8-4- TcR gamma/delta+. Western blot analysis indicated that the CH-L mAb identifies the same 56-58-kDa diffuse band in both T and natural killer cell (NK) clones. A minority of T cell clones also expressed other NK-related markers such as CD16, CD56 and CD94 and two clones also reacted with the anti-p58 mAb EB6. Interestingly, most clones displayed cytolytic activity in an anti-CD3 mAb-triggered redirected killing assay against the Fc gamma receptor+ P815 target cells and NK-like activity against K562 and Raji cells. In contrast, the IGROV-1 ovarian carcinoma cell line was resistant to cytolysis by all of these clones. Since p58 molecules have previously been shown to exert regulatory functions on NK-mediated lysis, we investigated whether anti-p58 mAb could also influence cytotoxicity mediated by CD3+p58+ T lymphocytes. Lysis of P815 target cells, triggered by anti-CD3 mAb, could be inhibited by anti-p58 mAb in 8 out of 12 cytolytic clones tested, while 4 clones were not inhibited. In addition, anti-p58 mAb enhanced the cytolytic activity of 3 clones against IGROV-1 and of 4 other clones against Raji target cells. Taken together, these data indicate that p58+ T cells express heterogeneous phenotypes and different forms of TcR and, in most instances, display cytolytic functions. Perhaps more importantly, the p58 molecule appears to modulate the cytolytic activity triggered via the CD3/TcR complex.
一种名为CH-L的新型抗p58单克隆抗体(mAb)已被用于鉴定共表达p58和CD3分子的一小部分T淋巴细胞。在双色免疫荧光分析中,CH-L + CD3 +细胞占外周血淋巴细胞的0.5%至6%(20名健康供体)。克隆分析表明,大多数CD3 + CH-L + T细胞克隆表达CD8 + 4 - T细胞受体(TcR)α/β +表型,而只有少数是CD8 - 4 + TcRα/β、CD8 - 4 - TcRα/β +或CD8 - 4 - TcRγ/δ +。蛋白质印迹分析表明,CH-L mAb在T细胞克隆和自然杀伤细胞(NK)克隆中均识别相同的56 - 58 kDa弥散条带。少数T细胞克隆还表达其他NK相关标志物,如CD16、CD56和CD94,并且有两个克隆也与抗p58 mAb EB6发生反应。有趣的是,大多数克隆在抗CD3 mAb触发的针对Fcγ受体 + P815靶细胞的重定向杀伤试验中表现出细胞溶解活性,并且对K562和Raji细胞具有NK样活性。相比之下,IGROV-1卵巢癌细胞系对所有这些克隆的细胞溶解具有抗性。由于先前已证明p58分子对NK介导的溶解发挥调节功能,我们研究了抗p58 mAb是否也能影响由CD3 + p58 + T淋巴细胞介导的细胞毒性。在12个细胞溶解克隆中,有8个克隆中抗CD3 mAb触发的P815靶细胞的溶解可被抗p58 mAb抑制,而4个克隆未被抑制。此外,抗p58 mAb增强了3个克隆对IGROV-1的细胞溶解活性以及另外4个克隆对Raji靶细胞的细胞溶解活性。综上所述,这些数据表明p58 + T细胞表达异质表型和不同形式的TcR,并且在大多数情况下表现出细胞溶解功能。也许更重要的是,p58分子似乎调节通过CD3/TcR复合物触发的细胞溶解活性。