Activation of alloreactive natural killer cells is resistant to cyclosporine

被引:24
作者
Petersson, E
Qi, ZQ
Ekberg, H
Ostraat, O
Dohlsten, M
Hedlund, G
机构
[1] LUND UNIV,MALMO GEN HOSP,DEPT EXPT RES,S-20502 MALMO,SWEDEN
[2] LUND UNIV,MALMO GEN HOSP,DEPT VASC & RENAL DIS,S-20502 MALMO,SWEDEN
[3] PHARMACIA & UPJOHN INC,LUND RES CTR,S-22007 LUND,SWEDEN
关键词
D O I
10.1097/00007890-199704270-00014
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. We have previously shown that cytotoxic T lymphocytes (CTL) with alloreactivity were induced when Wistar Furth (WF; RT1(u)) rats were immunized with allogeneic Brown Norway (BN; RTIn) cells. In contrast, when BN rats were immunized with WF cells, the allospecific response was confined to alloreactive natural killer (NK) cells, and no CTL activity was observed In this study, the effect of cyclosporine (CsA) on the activation of alloreactive NK cells in vivo was analyzed. Methods. Distinct peritoneal effector cells from rats immunized with allogenic cells with or without concomitant CsA and/or interleukin (IL) 2 treatment were tested for specific cytolytic activity. Furthermore, the presumptive role of NK cells in rejection immunity was addressed in a cardiac graft model. Results. The results showed that doses of CsA that completely inhibited the activation of alloreactive CTL, only marginally affected the activation of alloreactive NK cells. We also showed that CsA treatment failed to prolong graft survival in BN recipients of WF hearts. Treatment of BN rats with CsA/IL-2 during immunization with allogeneic WF cells resulted in concomitant induction of alloreactive NR cells and alloreactive CTL. Conclusions. We have demonstrated that CsA failed to suppress the activation of alloreactive NK cells. Consequently, the cardiac graft survival in the donor-recipient combination known to activate alloreactive NK cells was not significantly prolonged by CsA treatment, emphasizing the involvement of NK cells as effecters in organ rejection. Furthermore, the parallel emergence of alloreactive MC cells and CTL only in the presence of CsA/IL-2 indicated that CsA interfered with alloreactive NK cell-associated suppression of CTL activated by allogeneic tissue.
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页码:1138 / 1144
页数:7
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