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恒河猴中的自然杀伤细胞:裂解拉吉靶细胞的效应细胞特性。

Natural killer cells in rhesus monkeys: properties of effector cells which lyse Raji targets.

作者信息

Carver F M, Thomas J M

机构信息

Department of Surgery, East Carolina University, School of Medicine, Greenville, North Carolina 27834.

出版信息

Cell Immunol. 1988 Nov;117(1):56-69. doi: 10.1016/0008-8749(88)90076-7.

Abstract

Spontaneously occurring natural killer cell activity of rhesus monkey peripheral blood mononuclear cells was assayed against five human cell lines, three of which were Epstein-Barr virus (EBV) positive, including the human B cell line Raji. The lytic activity to Raji cells was high, significantly higher than to any other cell line tested. Raji cells are normally insensitive to spontaneous lysis by human NK cells, and the contrasting vigor of the rhesus monkey cytolytic activity to Raji prompted us to investigate the properties of this effector cell. We found the effector cell-mediating lysis of Raji to be nonadherent and phagocytic with lytic activity slightly enhanced in the E-rosette-forming cell (ERFC+) fraction and decreased in the ERFC- fraction. Further isolation of FcIgG receptor-positive and FcIgG receptor-negative subsets by rosetting resulted in significant enrichment of NK activity to Raji in the positive fraction and a loss of activity in the negative fraction. Depletion studies with various monoclonal antibodies (mAb's) confirmed that nearly all lytic activity was contained in the CD16+ (Leu 11b+) population, while subsets of effector cells expressed CD2 (9.6) and CD8 (OKT8). Depletion of CD4 (OKT4)-, HLADR (OKIa)-, or LFA1 (MAC-1)-positive populations failed to reduce NK activity. We compared the phenotypic properties of alloimmune effector cells exhibiting specificity for allogeneic donor targets with those exhibiting lysis of Raji targets. Results indicated that allospecific cytotoxic T lymphocytes expressed a CD16-, CD2+ phenotype, a pattern distinct from that of the effector cell population recognizing Raji targets. The presence of CD2 mAb's in the culture had no effect on NK lytic activity. In contrast, mAbs CD8 and Leu 11b were inhibitory. This would suggest a functional role for CD8 and FcIgG molecules in the lysis of Raji cells by rhesus effectors. In summary, these studies describe a distinct population of effector cells in the blood of rhesus monkeys which exhibit spontaneous lytic activity to Raji cells and exhibit the properties of NK cells.

摘要

测定了恒河猴外周血单个核细胞对五种人类细胞系的自发自然杀伤细胞活性,其中三种为爱泼斯坦-巴尔病毒(EBV)阳性,包括人类B细胞系拉吉(Raji)细胞系。对拉吉细胞的裂解活性很高,显著高于对其他任何测试细胞系的活性。拉吉细胞通常对人类自然杀伤细胞的自发裂解不敏感,而恒河猴对拉吉细胞的细胞溶解活性的显著差异促使我们研究这种效应细胞的特性。我们发现介导拉吉细胞裂解的效应细胞不具有黏附性和吞噬性,其裂解活性在E花环形成细胞(ERFC+)部分略有增强,而在ERFC-部分则降低。通过花环试验进一步分离FcIgG受体阳性和FcIgG受体阴性亚群,结果显示阳性部分对拉吉细胞的自然杀伤活性显著富集,而阴性部分活性丧失。用各种单克隆抗体(mAb)进行的去除研究证实,几乎所有的裂解活性都存在于CD16+(Leu 11b+)群体中,而效应细胞亚群表达CD2(9.6)和CD8(OKT8)。去除CD4(OKT4)阳性、HLADR(OKIa)阳性或LFA1(MAC-1)阳性群体未能降低自然杀伤活性。我们比较了对同种异体供体靶标具有特异性的同种免疫效应细胞与对拉吉靶标具有裂解作用的效应细胞的表型特性。结果表明,同种特异性细胞毒性T淋巴细胞表达CD16-、CD2+表型,这一模式与识别拉吉靶标的效应细胞群体不同。培养物中存在CD2 mAb对自然杀伤裂解活性没有影响。相反,mAb CD8和Leu 11b具有抑制作用。这表明CD8和FcIgG分子在恒河猴效应细胞对拉吉细胞的裂解中具有功能性作用。总之,这些研究描述了恒河猴血液中一种独特的效应细胞群体,它们对拉吉细胞表现出自发裂解活性,并具有自然杀伤细胞的特性。

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