Ectopically expressed PIR-B on T cells constitutively binds to MHC class I and attenuates T helper type 1 responses
Ectopically expressed PIR-B on T cells constitutively binds to MHC class I and attenuates T helper type 1 responses
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DOI：
10.1093/intimm/dxp081
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发表时间：
2009-10-01
影响因子：
4.4
通讯作者：
Takai, Toshiyuki
中科院分区：
文献类型：
--
作者：
Imada, Michiyo;Masuda, Kyoko;Takai, Toshiyuki
活化的成熟T细胞诱导各种抑制性受体，这些抑制性受体参与维持对反式作用配体的外周耐受。有趣的是，成对的Ig样受体（PIR）-B，一种在B细胞和髓样细胞上的抑制性MHC I类受体，可能参与调节早期T细胞发育，因为在前胸腺T/NK祖细胞上检测到PIR的表位，但在胸腺细胞或成熟T细胞上未检测到。我们假设PIR-B不仅是T细胞发育的调节因子，而且如果在成熟T细胞上表达也是有害的。在这里，我们证明，使用PIR-B缺陷的胎儿，PIR-B确实表达的T细胞祖细胞，但未能确定其在发展中的独特作用。胸腺细胞和成熟T细胞中PIR-B的强制表达也不会导致发育异常。然而，在抗原或同种异体刺激后，具有异位PIR-B的外周T细胞显示出降低的T-h 1型应答，这是由于PIR-B与同一细胞表面上的MHC I类的组成性结合抑制了近端TCR信号传导。我们的研究结果表明，PIR-B与顺式相互作用的MHC I类T细胞的表达是严格禁止在外周，以确保迅速的免疫应答。
Activated mature T cells induce various inhibitory receptors implicated in maintaining peripheral tolerance in response to the trans-acting ligands. Interestingly, paired Ig-like receptor (PIR)-B, an inhibitory MHC class I receptor on B cells and myeloid cells, could be involved in regulating early T cell development because epitope for PIR is detected on pre-thymic T/NK progenitors but not on thymocytes or mature T cells. We hypothesized that PIR-B is not only a regulator for T cell development but is also detrimental if expressed on mature T cells. Here we demonstrated, using PIR-B-deficient fetuses, that PIR-B is indeed expressed on the T cell progenitors but failed to identify its distinctive roles in the development. Forced expression of PIR-B in thymocytes and mature T cells also resulted in no abnormalities in development. However, upon antigenic or allogeneic stimulation, peripheral T cells with the ectopic PIR-B showed reduced T-h type 1 responses due to the suppression of proximal TCR signaling by constitutive binding of PIR-B to MHC class I on the same cell surface. Our findings suggest that T cell expression of PIR-B with the cis-interacting MHC class I is strictly prohibited in periphery so as to secure prompt immune responses.