Tomkinson B E, Maziarz R, Sullivan J L
Department of Pediatrics, University of Massachusetts Medical School, Worcester 01655.
J Immunol. 1989 Jul 15;143(2):660-70.
Primary infection with EBV during acute infectious mononucleosis (IM) is associated with a cytotoxic response against allogeneic target cells. C depletion with anti-CD3 (OKT3) and anti-CD8 (OKT8) mAb decreased the allogeneic cytolysis of two EBV-infected lymphoblastoid cell lines (LCL) by 96% and 89%, respectively. Complement depletion with the NK cell-specific mAb Leu-11b and NKH-1a resulted in only a slight decrease (less than 35%) in the lysis of these LCL. mAb inhibition studies with OKT3 and OKT8 inhibited the allogeneic lysis of two LCL by 87% and 82%, respectively. The alloreactive cytotoxic response was strongly inhibited by mAb specific for MHC class I determinants (W6/32, 65% inhibition and BBM.1, 58% inhibition). Acute IM lymphocytes lysed the allogeneic EBV-negative cell lines HSB2 (45%) and HTLV-1 T cell lines (16%). NK cell-depleted lymphocytes from an acute IM patient demonstrated preferential lysis of K562 transfected with human HLA-A2 (73%) compared with the K562 transfected control (20%). Cold target competition studies with allogeneic and autologous target and competitor LCL demonstrated no significant competitive inhibition between allogeneic and autologous cells. We interpret these results as evidence that 1) the acute IM-alloreactive cytotoxic response is mediated primarily by CTL; 2) these alloreactive CTL lyse allogeneic target cells irrespective of EBV antigenic expression; 3) MHC class I expression is sufficient for allogeneic recognition and lysis of target cells; 4) distinct effector CTL populations mediate lysis of autologous and allogeneic target cells; and 5) during acute IM, EBV infection results in the induction of both virus-specific and alloreactive CTL populations.
急性传染性单核细胞增多症（IM）期间初次感染EBV与针对同种异体靶细胞的细胞毒性反应有关。用抗CD3（OKT3）和抗CD8（OKT8）单克隆抗体消耗补体，分别使两种EBV感染的淋巴母细胞系（LCL）的同种异体细胞溶解减少了96%和89%。用NK细胞特异性单克隆抗体Leu-11b和NKH-1a消耗补体，导致这些LCL的裂解仅略有下降（小于35%）。用OKT3和OKT8进行的单克隆抗体抑制研究分别使两种LCL的同种异体裂解减少了87%和82%。针对MHC I类决定簇的单克隆抗体（W6/32，抑制率65%；BBM.1，抑制率58%）强烈抑制了同种异体反应性细胞毒性反应。急性IM淋巴细胞裂解了同种异体EBV阴性细胞系HSB2（45%）和HTLV-1 T细胞系（16%）。与K562转染对照（20%）相比，急性IM患者NK细胞耗竭的淋巴细胞对转染人HLA-A2的K562表现出优先裂解（73%）。用同种异体和自体靶细胞及竞争LCL进行的冷靶竞争研究表明，同种异体和自体细胞之间没有明显的竞争抑制作用。我们将这些结果解释为以下证据：1）急性IM同种异体反应性细胞毒性反应主要由CTL介导；2）这些同种异体反应性CTL裂解同种异体靶细胞，而不考虑EBV抗原表达；3）MHC I类表达足以实现对靶细胞的同种异体识别和裂解；4）不同的效应CTL群体介导自体和同种异体靶细胞的裂解；5）在急性IM期间，EBV感染导致病毒特异性和同种异体反应性CTL群体的诱导。
