Mason A, Bernard A, Smyth M J, Ortaldo J R
Laboratory of Experimental Immunology, National Cancer Institute-Frederick Cancer Research and Development Center 21702-1201.
Eur Cytokine Netw. 1991 Jan-Feb;2(1):31-7.
CD2 is a differentiation marker present on T cells and NK cells. Cytotoxic T lymphocytes (CTL) can be activated by antibodies directed against the CD3/T-cell receptor complex and CD2 structures; however, the role of CD2 in regulation of CD3- large granular lymphocyte (LGL) functions has only recently been studied. Anti-CD2 monoclonal antibodies (mAbs) may be either augmenting or inhibitory and T-cell activation via the CD2 molecule occurs only when mAb binds defined combinations of the CD2 epitopes. Since LGL can be activated by a single stimulus (e.g., IL-2) to proliferate, produce IFN gamma, and increase their cytolytic potential, these functions were chosen to examine the effects of the anti-CD2 mAb and its combinations. Anti-CD2 mAb (D66, GT2, and X11-1) were incubated with LGL for various times in the absence or presence of IL2 and IFN gamma production was monitored. Single anti-CD2 mAb treatment demonstrated minimal augmentation of IFN gamma production. However, combinations of anti-CD2 (9.6) and the other anti-CD2 mAb resulted in a significant, synergistic enhancement of the IFN gamma production. Anti-CD2 mAb treatment appeared to inhibit production generated by optimal doses of IL-2 (1,000 U/ml). The effect of anti-CD2 mAb on IFN gamma production parallel their effects on LGL NK and LAK activity. These data suggested that mAb against the CD2 molecule were important in regulating LGL functions in the absence of a functional CD3 receptor in LGL.(ABSTRACT TRUNCATED AT 250 WORDS)
CD2是一种存在于T细胞和自然杀伤细胞(NK细胞)上的分化标志物。细胞毒性T淋巴细胞(CTL)可被针对CD3/T细胞受体复合物和CD2结构的抗体激活;然而,CD2在调节CD3大颗粒淋巴细胞(LGL)功能中的作用直到最近才被研究。抗CD2单克隆抗体(mAb)可能具有增强或抑制作用,并且只有当mAb结合CD2表位的特定组合时,才会通过CD2分子发生T细胞激活。由于LGL可被单一刺激(如白细胞介素-2)激活以增殖、产生γ干扰素并增强其细胞溶解潜能,因此选择这些功能来研究抗CD2 mAb及其组合的作用。在不存在或存在白细胞介素-2的情况下,将抗CD2 mAb(D66、GT2和X11-1)与LGL孵育不同时间,并监测γ干扰素的产生。单独使用抗CD2 mAb治疗显示γ干扰素产生的增强作用最小。然而,抗CD2(9.6)与其他抗CD2 mAb的组合导致γ干扰素产生显著的协同增强。抗CD2 mAb治疗似乎抑制了最佳剂量白细胞介素-2(1000 U/ml)产生的γ干扰素。抗CD2 mAb对γ干扰素产生的影响与其对LGL自然杀伤和淋巴因子激活的杀伤细胞(LAK)活性的影响相似。这些数据表明,在LGL缺乏功能性CD3受体的情况下,针对CD2分子的mAb在调节LGL功能方面很重要。(摘要截短于250字)