HLA class I-specific inhibitory receptors in human T lymphocytes:: Interleukin 15-induced expression of CD94/NKG2A in superantigen- or alloantigen-activated CD8+ T cells
HLA class I-specific inhibitory receptors in human T lymphocytes:: Interleukin 15-induced expression of CD94/NKG2A in superantigen- or alloantigen-activated CD8+ T cells
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DOI：
10.1073/pnas.95.3.1172
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发表时间：
1998-02-03
影响因子：
11.1
通讯作者：
Moretta, L
中科院分区：
文献类型：
--
作者：
Mingari, MC;Ponte, M;Moretta, L
一小部分人类 T 淋巴细胞（主要是 CD8+）表达自然杀伤细胞典型的 HLA I 类分子受体（自然杀伤受体或 NKR），可抑制 T 细胞受体介导的功能。在此，我们分析了体外 T 细胞响应超抗原或同种异体细胞表达 NKR 的可能机制。我们表明，在白细胞介素 15 (IL-15) 存在的情况下，响应中毒性休克综合征毒素 1 的 T 细胞（NKR+细胞）从头表达 CD94，CD94 是异二聚体 NKR 的一部分，对不同的 HLA I 类等位基因具有广泛的特异性。当细胞放入培养物后不久添加IL-15时，出现最大CD94表达，并且CD94表达在添加IL-15后4-6天开始。尽管CD4(+)和CD8(+)细胞均表达CD94，但NKG2A（即CD94/NKG2A抑制性NKR的其他成分）的同时表达仅限于CD8(+)细胞，在IL-15存在的混合淋巴细胞培养物中激活的T细胞群中获得了类似的数据，CD94/NKG2A的表达导致混合淋巴细胞同种异体特异性细胞溶解活性受损值得注意的是，通过添加抗 CD94 mAb，即通过掩蔽抑制性 NKR，可以恢复细胞溶解。
A fraction of human T lymphocytes, predominantly CD8(+), express receptors for HLA class I molecules typical of natural killer cells (natural killer receptors or NKRs) that inhibit T cell receptor-mediated functions. Herein, we analyzed possible mechanism(s) leading to the expression of NKRs by T cells responding to superantigens or allogeneic cells in vitro, We show that, in the presence of interleukin 15 (IL-15), T cells (depleted of NKR+ cells) responding to toxic shock syndrome toxin 1 de novo express CD94, a molecule that is part of a heterodimeric NKR with a broad specificity for different HLA class I alleles. Maximal CD94 expression occurred when IL-15 was added shortly after the cells were placed into culture, and CD94 expression started 4-6 days after addition of IL-15. Although both CD4(+) and CD8(+) cells expressed CD94, the simultaneous expression of NKG2A (i.e., the other component of the CD94/NKG2A inhibitory NKR) was confined to CD8(+) cells, Similar data were obtained in T cell populations activated in mixed lymphocyte cultures in the presence of IL-15, The expression of CD94/NKG2A led to an impairment of allo-specific cytolytic activity by mixed lymphocyte culture-derived T cell populations or clones, Remarkably, cytolysis could be restored by the addition of anti-CD94 mAb, i.e., by masking the inhibitory NKRs.