INDIRECT ALLORECOGNITION OF PLATELETS BY T-HELPER CELLS DURING PLATELET TRANSFUSIONS CORRELATES WITH ANTI-MAJOR HISTOCOMPATIBILITY COMPLEX ANTIBODY AND CYTOTOXIC T-LYMPHOCYTE FORMATION
INDIRECT ALLORECOGNITION OF PLATELETS BY T-HELPER CELLS DURING PLATELET TRANSFUSIONS CORRELATES WITH ANTI-MAJOR HISTOCOMPATIBILITY COMPLEX ANTIBODY AND CYTOTOXIC T-LYMPHOCYTE FORMATION
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DOI：
10.1182/blood.v86.2.805.bloodjournal862805
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发表时间：
1995-07-15
期刊：
影响因子：
20.3
通讯作者：
FREEDMAN, J
中科院分区：
文献类型：
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作者：
SEMPLE, JW;SPECK, ER;FREEDMAN, J
为了研究血小板诱导的同种异体免疫的细胞免疫学，建立了鼠输血模型，将来自C57 BL/6（H-2（B））供体小鼠的2 × 10（8）血小板或10（3）白细胞每周输注给BALB/c（H-2（d））受体小鼠，抗供者主要组织相容性复合体（MHC）第5次输注血小板时，流式细胞仪检测到I类同种抗体，而仅输注白细胞时，未检测到同种抗体。体外试验表明，小鼠H-2（B）血小板对MHC 1类分子表达呈阳性，但其膜上缺乏MHC II类分子，当与初始H-2（d）脾细胞孵育时，不能刺激增殖或细胞因子产生。然而，在体内，血小板输注诱导两种不同的细胞介导的反应模式。首先，在最初的输血和同种抗体形成之前，有诱导T细胞无能，其特征是受体T细胞不能应答刀豆球蛋白A（ConA）或在抗供体混合淋巴细胞反应（MLR）中增殖，以及抑制自然杀伤（NK）细胞活性。这种无反应性与一氧化氮（NO）依赖性细胞毒性和白细胞介素-1（IL-1）产生的短暂增加有关。其次，一旦产生同种抗体，观察到抗供体CD 8（+）细胞毒性T淋巴细胞（CTL）和NK细胞应答显著增加。此时，在7天抗原呈递细胞（APC）试验中，当受体脾细胞耗尽CD 8（+）T细胞并仅与供体血小板孵育时，增殖和IL-2产生增加。当输注10（3）个同种异基因白细胞时，未观察到这些细胞反应。因此，结果表明，白细胞减少的血小板输注诱导受体小鼠的抗供体MHC抗体和CD 8（+）CTL反应。与此同时，在同基因APC存在的情况下与供体血小板孵育时，输血诱导受体CD 4（+）T细胞活化，这是一种与同种抗体产生时间相关的间接识别途径。(C)1995年，美国血液学会。
To study the cellular immunology of platelet-induced alloimmunization, a murine transfusion model was developed, BALB/c (H-2(d)) recipient mice were transfused weekly with 2 x 10(8) platelets or 10(3) leukocytes from C57BL/6 (H-2(b)) donor mice, Recipient antidonor major histocompatibility complex (MHC) class I alloantibodies could be detected in flow cytometric assays by the fifth platelet transfusion, In contrast, when leukocytes only were transfused, alloantibodies were not detected. In vitro assays demonstrated that murine H-2(b) platelets were positive for MHC class 1 expression but lacked MHC class II molecules on their membranes and were unable to stimulate proliferation or cytokine production when incubated with naive H-2(d) spleen cells. In vivo, however, platelet transfusions induced two distinct patterns of cell-mediated reactivity. First, during the initial transfusions and before alloantibody formation, there was induction of T-cell anergy, characterized by the inability of recipient T cells to respond to Concanavalin A (ConA) or to proliferate in an antidonor mixed lymphocyte reaction (MLR), together with suppressed natural killer (NK) cell activity. This unresponsiveness was associated with a transient increase in nitric oxide (NO)-dependent cytotoxicity and interleukin-1 (IL-1) production. Second, once alloantibodies developed, significantly increased antidonor CD8(+) cytotoxic T lymphocyte (CTL) and NK cell responses were observed. At this time, when recipient spleen cells were depleted of CD8(+) T cells and incubated with only donor platelets in 7-day antigen-presenting cell(APC) assays, enhanced proliferation and IL-2 production occurred. These cellular responses were not seen when 10(3) allogeneic leukocytes were transfused. Thus, the results suggest that leukoreduced platelet transfusions induce antidonor MHC antibodies and CD8(+) CTL responses in recipient mice. At the same time, the transfusions induced recipient CD4(+) T-cell activation when incubated with donor platelets in the presence of syngeneic APCs, an indirect recognition pathway that correlates with the time of alloantibody production.(C) 1995 by The American Society of Hematology.