Role of natural killer cells in the rejection process of corneal allografts in rats
Role of natural killer cells in the rejection process of corneal allografts in rats
复制标题
DOI：
10.1097/01.tp.0000114964.07637.b4
复制
发表时间：
2004-03-15
期刊：
影响因子：
6.2
通讯作者：
Leclercq, G
中科院分区：
文献类型：
--
作者：
Claerhout, I;Kestelyn, P;Leclercq, G
背景角膜移植排斥反应是角膜移植失败的主要原因，其确切机制尚不清楚。本研究通过检测大鼠角膜移植术后不同时间的房水（AH）细胞浸润，探讨自然杀伤（NK）细胞在角膜移植排斥反应中的作用。在移植前和移植后不同时间点对AH和下颌下引流淋巴结（DLN）细胞进行流式细胞术分析。此外，我们还对角膜排斥反应过程中AH中的细胞进行了功能性细胞毒性试验。我们证明了异基因角膜移植后AH中不同造血亚群的绝对细胞数逐渐增加。CD 3（-）CD 4（+）细胞，主要是单核细胞和巨噬细胞，是移植后2天的主要亚群，随后是CD 4（+）T细胞、CD 8（+）T细胞、CD 161（+）T细胞和NK细胞的连续相对增加。NK和CD 161（+）T细胞的百分比比DLN高10- 15倍，表明这些细胞的局部扩增。与DLN NK细胞相比，更高百分比的NK细胞是CD 8阴性的。AH细胞特异性裂解同种异体细胞，这种杀伤作用主要是NK细胞所致，而不是CD 4（+）或CD 8（+）T淋巴细胞所致。这些结果证实了CD 4（+）细胞在同种异体角膜移植排斥反应过程中的关键作用，并暗示NK细胞可能是排斥反应的介质。
Background. The exact mechanism of human corneal allograft rejection, which is the major cause of corneal transplant failure, remains unclear. We investigated the role of natural killer (NK) cells in rat corneal allograft rejection by examining the aqueous humor (AH) cell infiltrate on different postoperative days.Methods. Flow cytometric analysis was performed on the AH and submandibular draining lymph node (DLN) cells before transplantation and at different time points thereafter. In addition, we performed functional cytotoxicity assays with cells present in the AH during corneal rejection.Results. We demonstrated a gradual increase in the absolute cell number of different hematopoietic sub-populations in the AH after allogeneic cornea transplantation. CD3(-)CD4(+) cells, mainly monocytes and macrophages, were the predominant subpopulation 2 days after transplantation, followed by a successive relative increase of CD4(+) T cells, CD8(+) T cells, CD161(+) T cells, and NK cells. NK and CD161(+) T cells were present at a 10- to 15-fold higher percentage than in the DLN, suggestive of local expansion of these cells. A higher percentage of NK cells were CD8-negative compared with DLN NK cells. AH cells specifically lysed allogeneic cells, and this cytotoxicity was mainly attributable to NK cells but not to CD4(+) or CD8(+) T lymphocytes.Conclusion. These results confirm the crucial role of CD4(+) cells in the allogeneic corneal graft rejection process and implicate NK cells as possible mediators of the rejection.