Soluble HLA-A,-B,-C and -G molecules induce apoptosis in T and NKCD8+ cells and inhibit cytotoxic T cell activity through CD8 ligation
Soluble HLA-A,-B,-C and -G molecules induce apoptosis in T and NKCD8+ cells and inhibit cytotoxic T cell activity through CD8 ligation
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DOI：
10.1002/immu.200390015
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发表时间：
2003-01-01
影响因子：
5.4
通讯作者：
Puppo, F
中科院分区：
文献类型：
--
作者：
Contini, P;Ghio, M;Puppo, F
有令人信服的证据表明，可溶性HLA-A，-B,-C （sHLA-A,-B,-C）和可溶性HLA-G （sHLA-G）抗原可以诱导CD8（+）活化的T细胞凋亡，尽管关于sHLA-A，-B，-C抗原和sHLA-G抗原诱导细胞凋亡的机制缺乏和相互矛盾的信息。在本研究中，我们比较了sHLA-A、-B、-C抗原与sHLA-G1抗原在CD8(+) T淋巴细胞和CD8+ NK细胞中的诱导凋亡能力。此外，我们还比较了sHLA-A、-B、-C抗原和sHLA-G1抗原对ebv特异性CD8（+）细胞毒性T淋巴细胞（CTL）活性的抑制作用。sHLA分子从转染了经典或非经典HLA I类抗原的基因的HLA I类阴性细胞的血清和上清液中纯化。经典的和非经典的sHLA I类分子都能在缺乏T细胞受体的CD8(+) T淋巴细胞和CD8(+) NK细胞中触发细胞凋亡，它们的凋亡效力是相似的。sHLA-A,-B，-C和sHLA-G1的结合。通过Fas/sFasL相互作用导致Fas配体（FasL）上调、可溶性FasL （sFasL）分泌和CD8+细胞凋亡。此外，经典和非经典sHLA I类分子抑制ebv特异性CD8(+) CTL的细胞毒活性。由于正常血清中可检测到的sHLA- g分子数量明显低于sHLA- a、-B、-C分子，因此从血清中纯化的sHLA I类分子的免疫调节作用可能主要归因于经典HLA I类抗原。就这些发现的潜在体内相关性而言，我们认为经典的sHLA I类分子可能在以免疫系统激活和sHLA- a，-B，-C血清水平升高为特征的临床情况下发挥主要的免疫调节作用。相反，非经典HLA I类分子可能在妊娠和某些肿瘤疾病等以sHLA-G水平升高为特征的特殊情况下发挥免疫调节作用。
There is convincing evidence that soluble HLA-A,-B,-C (sHLA-A,-B,-C) and soluble HLA-G (sHLA-G) antigens can induce apoptosis in CD8(+) activated T cells although there is scanty and conflicting information about the mechanism(s) by which sHLA-A,-B,-C antigens and sHLA-G antigens induce apoptosis. In this study we have compared the apoptosis-inducing ability of sHLA-A,-B,-C antigens with that of sHLA-G1 antigens in CD8(+) T lymphocytes and CD8+ NK cells. Furthermore we have compared the inhibitory effect of sHLA-A,-B,-C antigens and of sHLA-G1 antigens on the activity of EBV-specific CD8(+) cytotoxic T lymphocytes (CTL). sHLA molecules were purified from serum and from the supernatant of HLA class I-negative cells transfected with one gene encoding either classical or non-classical HLA class I antigens. Both classical, and non-classical sHLA class I molecules trigger apoptosis in CD8(+) T lymphocytes and in CD8(+) NK cells, which lack the T cell receptor, and their apoptotic potency is comparable. The binding of sHLA-A,-B,-C and sHLA-G1. molecules to CD8 leads to Fas ligand (FasL) up-regulation, soluble FasL (sFasL) secretion and CD8+ cell apoptosis by Fas/sFasL interaction. Moreover, classical and non-classical sHLA class I molecules inhibit the cytotoxic activity of EBV-specific CD8(+) CTL. As the amount of sHLA-G molecules detectable in normal serum is significantly lower than that of sHLA-A,-B,-C molecules, the immunomodulatory effects of sHLA class I molecules purified from serum are likely to be mainly attributable to classical HLA class I antigens. As far as the potential in vivo relevance of these findings is concerned, we suggest that classical sHLA class I molecules may play a major immunoregulatory role in clinical situations characterized by activation of the immune system and elevated sHLA-A,-B,-C serum levels. In contrast, non-classical HLA class I molecules may exert immunomodulatory effects in particular conditions characterized by elevated sHLA-G levels such as pregnancy and some neoplastic diseases.