IMMUNE-MECHANISMS IN ORGAN ALLOGRAFT-REJECTION .5. PIVOTAL ROLE OF THE CYTOTOXIC-SUPPRESSOR T-CELL SUBSET IN THE REJECTION OF HEART GRAFTS BEARING ISOLATED CLASS-I DISPARITIES IN THE INBRED RAT
IMMUNE-MECHANISMS IN ORGAN ALLOGRAFT-REJECTION .5. PIVOTAL ROLE OF THE CYTOTOXIC-SUPPRESSOR T-CELL SUBSET IN THE REJECTION OF HEART GRAFTS BEARING ISOLATED CLASS-I DISPARITIES IN THE INBRED RAT
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DOI：
10.1097/00007890-198511000-00014
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发表时间：
1985-01-01
期刊：
影响因子：
6.2
通讯作者：
MARGHESCO, DM
中科院分区：
文献类型：
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作者：
LOWRY, RP;FORBES, RDC;MARGHESCO, DM
通过过继性移植评估了携带分离的主要组织相容性复合体（MHC）亚区rt1a编码的I类差异的心脏移植物对排斥反应的细胞需求。亚致死辐射（780拉德）（PVG）次。WF) F1受者接受PVG-RT1r1心脏移植后，用同源供者的脾脏细胞选择性重建，这些供者之前接受过两次连续的PVG-RT1r1皮肤移植致敏。PVG-RT1r1心脏移植在10倍重构的受者中发生急性排斥反应。未分离免疫脾细胞106个（7-9天，n = 6）或接种5次。SIg+细胞（10-13天，n = 5）缺失，但细胞毒性T细胞及其前体（0X8+）的进一步缺失导致移植物存活时间明显延长（n = 4,4倍）。106个细胞，45-67天)。减少重组接种4次。106到2.5倍。106个脾脏细胞（0X8-, SIg-）将移植物存活时间延长至未重组受体（通常为100天）。进一步的研究确定PVG- rt1r1心脏移植物在纯合子PVG受体中延长存活的免疫学基础。尽管未处理PVG的淋巴样细胞在与辐照PVG- rt1r1共培养时未能增殖（刺激指数[SI] 1.01, P = NS），大量培养产生但弱且可变的CTL，但在相同条件下，特异性敏化PVG的淋巴样细胞增殖（SI 4.25, P < 0.001）并产生更大的细胞毒性T淋巴细胞（CTL）活性（P < 0.001），因此，强烈表明，在这种菌株组合中延长的心脏移植存活与低CTL前体频率有关。此外，尽管PVG- rt1r1心脏移植在10-12天（n = 3）被（PVG x WF）F11受体排斥，（PVG- rt1r1）次。F2 .fwdarw WF)。(PVG同学。尽管存在相同的同种免疫反应，但WF)F1心脏移植物（RT1Aa差异）存活了100天，这与（pvg - RT1Aa）的敏感性降低了0.1倍有关。WF)F1靶细胞被CTL裂解。因此，这些数据有力地表明，CTL在i类异种心脏移植排斥反应中的关键作用实际上与其直接细胞介导的细胞溶解功能有关。
The cellular requirements for rejection of heart grafts bearing isolated major histocompatibility complex (MHC) subregion RT1A-encoded class I disparities was assessed by adoptive transfer. Sublethally irradiated (780 rads) (PVG .times. WF) F1 recipients of irradiated PVG-RT1r1 heart grafts were selectively reconstituted with spleen cells from syngeneic donors previously sensitized with two sequential PVG-RT1r1 skin grafts. PVG-RT1r1 heart grafts were rejected acutely in recipients reconstitued with 10 .times. 106 unfractionated immune spleen cells (7-9 days, n = 6) or inocula (5 .times. 106 cells) depleted of SIg+ cells (10-13 days, n = 5), but additional depletion of cytotoxic T cells and their precursors (0X8+) resulted in marked prolongation of graft survival (n = 4, 4 .times. 106 cells, 45-67 days). Reducing the reconstituting inocula from 4 .times. 106 to 2.5 .times. 106 spleen cells (0X8-, SIg-) prolonged graft survival to that observed in unreconstituted recipients (generally > 100 days). Additional studies were performed of define the immunologic basis for prolonged survival of PVG-RT1r1 heart grafts in homozygous PVG recipients. Although lymphoid cells of naive PVG failed to proliferate (stimulation index [SI] 1.01, P = NS) on coculture with irradiated PVG-RT1r1, bulk cultures yielding but weak and variable CTL generation, lymphoid cells from specifically sensitized PVG proliferated (SI 4.25, P < 0.001) and generated greater cytotoxic T lymphocyte (CTL) activity (P < .001) under identical conditions, strongly suggesting, therefore, that prolonged heart graft survival in this strain combination is related to low CTL precursor frequency. Further, though PVG-RT1r1 heart grafts were rejected in 10-12 days (n = 3) by (PVG x WF)F11 recipients, (PVG-RT1r1 .times. WF)F2 .fwdarw. (PVG .times. WF)F1 heart grafts (RT1Aa disparity) survived > 100 days dispite an equivalent alloimmune response, and this was shown to correlate with a reduced sensitivity of (PVG-RT1r1 .times. WF)F1 target cells to lysis by CTL. These data, therefore, strongly suggest that the pivotal role of CTL in the rejection of class-I-disparate heart grafts is, in fact, related to their function in direct cell-mediated cytolysis.