Human effector memory CD4+ T cells directly recognize allogeneic endothelial cells in vitro and in vivo
Human effector memory CD4+ T cells directly recognize allogeneic endothelial cells in vitro and in vivo
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DOI：
10.4049/jimmunol.179.7.4397
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发表时间：
2007-10-01
影响因子：
4.4
通讯作者：
Pober, Jordan S.
中科院分区：
文献类型：
--
作者：
Shiao, Stephen L.;Kirkiles-Smith, Nancy C.;Pober, Jordan S.
循环同种异体反应性人类记忆T细胞的频率与同种异体移植排斥反应相关。记忆T细胞可分为效应记忆（T- em）和中枢记忆（T- cm）细胞亚群，但它们在同种异体移植排斥反应中的具体作用尚不清楚。我们报道CD4(+) T- em (CD45RO(+)CCR7（-)CD62L(-)）可以很容易地过继转移到C.B-17 SCID/bg小鼠体内，并介导与T细胞供体异体的血管化人皮移植物中人内皮细胞（EC）的破坏。相比之下，CD4+ T-CM (CD45RO(+)CCR7（+)CD62L(+)）转移效率低下，不介导EC损伤。在体外，CD4(+) T-EM对异基因ECs的反应比T-CM分泌更多的ifn - γ。相比之下，T-EM和T-CM在对同种异体单核细胞（Mo）的反应中分泌相当数量的ifn - γ。在相同的培养中，T-EM和T-CM都产生IL-2并对ifn - γ处理的异体人EC或Mo产生反应，但T-CM在两种检测中反应更强烈。阻断LFA-3可强烈抑制同种异体EC培养的CD4(+) T-EM分泌IL-2和ifn - γ，但仅能最低限度地抑制同种异体Mo的反应。阻断CD80和CD86可强烈抑制同种异体EC或Mo对IL-2的反应，但不能抑制ifn - γ的产生。传导EC表达B7-2可增强同种异体T-EM产生IL-2，但不能增强ifn - γ。我们得出的结论是，人类CD4(+) T-EM通过分泌ifn - γ直接识别异体EC并对其产生反应，并且这种反应依赖于CD2而不是CD28。与EC激活效应功能一致，人CD4+ T-EM可介导体内异体EC损伤。
The frequency of circulating alloreactive human memory T cells correlates with allograft rejection. Memory T cells may be divided into effector memory (T-EM) and central memory (T-CM) cell subsets, but their specific roles in allograft rejection are unknown. We report that CD4(+) T-EM (CD45RO(+)CCR7(-)CD62L(-)) can be adoptively transferred readily into C.B-17 SCID/bg mice and mediate the destruction of human endothelial cells (EC) in vascularized human skin grafts allogeneic to the T cell donor. In contrast, CD4+ T-CM (CD45RO(+)CCR7(+)CD62L(+)) are inefficiently transferred and do not mediate EC injury. In vitro, CD4(+) T-EM secrete more IFN-gamma within 48 It in response to allogeneic ECs than do T-CM. In contrast, T-EM and T-CM secrete comparable amounts of IFN-gamma in response to allogeneic monocytes (Mo). In the same cultures, both T-EM and T-CM produce IL-2 and proliferate in response to IFN-gamma-treated allogeneic human EC or Mo, but T-CM respond more vigorously in both assays. Blockade of LFA-3 strongly inhibits both IL-2 and IFN-gamma secretion by CD4(+) T-EM cultured with allogeneic EC but only minimally inhibits responses to allogeneic Mo. Blockade of CD80 and CD86 strongly inhibits IL-2 but not IFN-gamma production by in response to allogeneic EC or Mo. Transduction of EC to express B7-2 enhances allogeneic T-EM production of IL-2 but not IFN-gamma. We conclude that human CD4(+) T-EM directly recognize and respond to allogeneic EC in vitro by secreting IFN-gamma and that this response depends on CD2 but not CD28. Consistent with EC activation of effector functions, human CD4+ T-EM can mediate allogeneic EC injury in vivo.