HAPLOTYPE-SPECIFIC SUPPRESSION OF CYTO-TOXIC T-CELL INDUCTION BY ANTIGEN INAPPROPRIATELY PRESENTED ON T-CELLS
HAPLOTYPE-SPECIFIC SUPPRESSION OF CYTO-TOXIC T-CELL INDUCTION BY ANTIGEN INAPPROPRIATELY PRESENTED ON T-CELLS
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DOI：
10.1084/jem.157.1.141
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发表时间：
1983-01-01
影响因子：
15.3
通讯作者：
BEVAN, MJ
中科院分区：
文献类型：
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作者：
FINK, PJ;WEISSMAN, IL;BEVAN, MJ
为了在5天混合淋巴细胞培养中检测对次要组织相容性（H）抗原的强细胞毒性T淋巴细胞（CTL）应答，有必要使用已在体内用抗原携带细胞引发的应答者。已经表明，小H特异性CTL可以在体内直接由外源脾细胞和通过在宿主抗原呈递细胞上呈递外源小H抗原来引发。后一种途径在交叉引发现象中是明显的，其中H-2杂合的（A × B）B）预先用少量H-不同的H-2A（A“）脾细胞注射2周的F1小鼠产生H-2A-和H-2B-限制的少量H-特异性CTL。在F1小鼠中直接与交叉致敏未成年人的动力学研究中，发现未成年人H-不同T细胞实际上抑制了能够识别它们的原始CTL的诱导。在用活的A“脾细胞注射后3-6天从F1小鼠测量的CTL活性在很大程度上是H-2B限制的。H-2A限制性反应恢复，以至于早在注射后8-10天就在小鼠中检测到大致相等的A限制性活性和B限制性活性。这种暂时的低反应性不是由全身性免疫抑制引起的;它对那些在注射的脾细胞上的H-2抗原的背景下识别外来次要H抗原的CT 1是特异性的。介导这种抑制的注射的脾细胞是放射敏感性T细胞; Lyt-2+ T细胞在体内抑制CTL的诱导方面非常有效。似乎不需要注射的T细胞的移植物抗宿主反应，因为直接引发的CTL的抑制可以由完全耐受宿主H-2和次要H抗原的脾细胞介导。体外混合实验无法证明抑制作用。单倍型特异性抑制的几种可能的机制进行了讨论，包括响应CTL的否决细胞和响应CTL的体内隔离注射的脾细胞的失活。
To detect a strong cytotoxic T lymphocyte (CTL) response to minor histocompatibility (H) antigens in a 5 d [day] mixed lymphocyte culture, it is necessary to use a responder that has been primed in vivo with antigen-bearing cells. It has been shown that minor-H-specific CTL can be primed in vivo both directly by foreign spleen cells and by presentation of foreign minor H antigens on host antigen-presenting cells. This latter route is evident in the phenomenon of cross-priming, in which H-2 heterozygous (A .times. B)F1 mice injected 2 wk previously with minor H-different H-2A (A'') spleen cells generate both H-2A- and H-2B-restricted minor-H-specific CTL. In a study of the kinetics of direct- vs. cross-priming to minors in F1 mice, it was found that minor H-different T cells actually suppress the induction of virgin CTL capable of recognizing them. CTL activity measured from F1 mice 3-6 d after injection with viable A'' spleen cells is largely H-2B restricted. The H-2A-restricted response recovers such that roughly equal A- and B-restricted activity is detected in mice as early as 8-10 d postinjection. This temporary hyporeactivity does not result from generalized immunosuppression; it is specific for those CTl that recognize the foreign minor H antigen in the context of the H-2 antigens on the injected spleen cells. The injected spleen cells that mediate this suppression are radiosensitive T cells; Lyt-2+ T cells are highly efficient at suppressing the induction of CTL in vivo. No graft vs. host reaction by the injected T cells appears to be required, as suppression of direct-primed CTL can be mediated by spleen cells that are wholly tolerant of both host H-2 and minor H antigens. Suppression cannot be demonstrated by in vitro mixing experiments. Several possible mechanisms for haplotype-specific suppression are discussed, including inactivation of responding CTL by veto cells and in vivo sequestration of responding CTL by the injected spleen cells.