Petersson E, Ostraat O, Ekberg H, Hansson J, Simanaitis M, Brodin T, Dohlsten M, Hedlund G
Department of Tumor Immunology, Lund University, Sweden.
Cell Immunol. 1997 Jan 10;175(1):25-32. doi: 10.1006/cimm.1996.1031.
The ability of natural killer (NK) cells to recognize and reject transplants has so far been shown in hematopoietic grafts only. This study was designed to ascertain whether NK cells may also be involved in the rejection of transplanted organs. In most rat strain combinations, immunization with allogeneic cells induces a T cell response with cytotoxic T lymphocyte (CTL) activation. We have previously found one exception to this. In contrast to Wistar Furth rats (WF, RT1u), which manifest allospecific CTL activation in response to immunization with Brown Norway (BN, RT1n) cells, BN rats immunized with repeated intraperitoneal (i.p.) injections of allogeneic WF spleen cells manifest activation of alloreactive NK effector cells. The alloreactive NK cells were of the TCR-, CD3-, CD8+, and NKR-P1 intermediate phenotype and killed target cells with alloselectivity. In this study we used a heart transplantation model to study the rejection response of BN rats receiving WF grafts. NK cell infiltration was greater in WF hearts transplanted to BN recipients than in BN hearts transplanted to WF recipients. Furthermore, the extent of T cell infiltration was less in BN recipients. In WF rats transplanted with allogeneic BN hearts, CTL were activated in response to i.p. challenge with allogeneic BN cells, whereas BN rats transplanted with allogeneic WF hearts and i.p. challenged with allogeneic WF cells, manifested activation of alloreactive NK cells but no measurable activation of classic CTL. The alloreactive NK cells killed their allogeneic targets with specificity and with potency comparable to that of CTL. Furthermore, WF grafts were rejected in BN recipients as efficiently as were BN grafts in WF recipients. These results not only show cardiac allografts to be able to activate alloreactive NK cells, but also suggest that NK cells may be involved in the rejection of solid organ transplants and function as classic CTL in certain donor-recipient combinations.
迄今为止，自然杀伤（NK）细胞识别并排斥移植器官的能力仅在造血移植中得到证实。本研究旨在确定NK细胞是否也参与移植器官的排斥反应。在大多数大鼠品系组合中，用同种异体细胞免疫会诱导T细胞反应并激活细胞毒性T淋巴细胞（CTL）。我们之前发现了一个例外情况。与经Brown Norway（BN，RT1n）细胞免疫后表现出同种特异性CTL激活的Wistar Furth大鼠（WF，RT1u）不同，经腹腔（i.p.）反复注射同种异体WF脾细胞免疫的BN大鼠表现出同种反应性NK效应细胞的激活。同种反应性NK细胞具有TCR-、CD3-、CD8+和NKR-P1中间表型，并且能以同种选择性方式杀伤靶细胞。在本研究中，我们使用心脏移植模型来研究接受WF移植物的BN大鼠的排斥反应。移植到BN受体的WF心脏中的NK细胞浸润比移植到WF受体的BN心脏中的NK细胞浸润更严重。此外，BN受体中的T细胞浸润程度较低。在移植了同种异体BN心脏的WF大鼠中，经同种异体BN细胞腹腔攻击后CTL被激活，而移植了同种异体WF心脏并经同种异体WF细胞腹腔攻击的BN大鼠表现出同种反应性NK细胞的激活，但未检测到经典CTL的激活。同种反应性NK细胞能特异性地杀伤其同种异体靶细胞，其效力与CTL相当。此外，BN受体中WF移植物的排斥效率与WF受体中BN移植物的排斥效率相同。这些结果不仅表明心脏同种异体移植能够激活同种反应性NK细胞，还表明NK细胞可能参与实体器官移植的排斥反应，并在某些供体-受体组合中发挥经典CTL的作用。
