Imada Michiyo, Masuda Kyoko, Satoh Rumi, Ito Yumi, Goto Yoshiyuki, Matsuoka Takayuki, Endo Shota, Nakamura Akira, Kawamoto Hiroshi, Takai Toshiyuki
Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Int Immunol. 2009 Oct;21(10):1151-61. doi: 10.1093/intimm/dxp081. Epub 2009 Aug 14.
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.
活化的成熟T细胞可诱导多种抑制性受体，这些受体在响应反式作用配体时参与维持外周耐受。有趣的是，配对免疫球蛋白样受体（PIR）-B是B细胞和髓样细胞上的一种抑制性MHC I类受体，可能参与调节早期T细胞发育，因为在胸腺前T/NK祖细胞上可检测到PIR的表位，但在胸腺细胞或成熟T细胞上则检测不到。我们推测PIR-B不仅是T细胞发育的调节因子，而且如果在成熟T细胞上表达也会产生有害影响。在此，我们利用PIR-B缺陷型胎儿证明，PIR-B确实在T细胞祖细胞上表达，但未能确定其在发育中的独特作用。在胸腺细胞和成熟T细胞中强制表达PIR-B也未导致发育异常。然而，在抗原或同种异体刺激下，异位表达PIR-B的外周T细胞由于PIR-B与同一细胞表面的MHC I类分子组成性结合抑制近端TCR信号传导，导致1型辅助性T细胞（Th1）反应降低。我们的研究结果表明，在外周严格禁止T细胞表达与顺式相互作用的MHC I类分子结合的PIR-B，以确保迅速的免疫反应。
