Inhibition of cytolytic T lymphocyte proliferation by autologous CD4+/CD25+ regulatory T cells in a colorectal carcinoma patient is mediated by transforming growth factor-beta.
Inhibition of cytolytic T lymphocyte proliferation by autologous CD4+/CD25+ regulatory T cells in a colorectal carcinoma patient is mediated by transforming growth factor-beta.
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发表时间：
2002-09
期刊：
影响因子：
11.2
通讯作者：
R. Somasundaram;L. Jacob;R. Swoboda;L. Caputo;Hong-ping Song;S. Basak;D. Monos;D. Peritt;F. Marincola;Dewei Cai;B. Birebent;E. Bloome;Jin Kim;K. Berencsi;M. Mastrangelo;D. Herlyn
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作者：
R. Somasundaram;L. Jacob;R. Swoboda;L. Caputo;Hong-ping Song;S. Basak;D. Monos;D. Peritt;F. Marincola;Dewei Cai;B. Birebent;E. Bloome;Jin Kim;K. Berencsi;M. Mastrangelo;D. Herlyn
癌症患者经常发展CTL，其裂解培养物中的自体肿瘤细胞。然而，尽管存在CTL，肿瘤仍可以在体内进展。已经报道了下调CTL功能的各种机制。在这项研究中，CD 4 +/CD 25+调节性T细胞在CTL诱导和CTL增殖中的作用在CRC患者中进行了研究。CD 4+细胞毒性和调节性T细胞系来源于混合淋巴细胞肿瘤培养物中同一患者的外周血单核细胞。细胞毒性T细胞系和克隆衍生物特异性裂解自体肿瘤细胞，但不裂解B淋巴细胞。CTL克隆仅裂解HLA-A1匹配的同种异体CRC细胞。该克隆产生IFN-γ和TNF-α。调节性CD 4 +/CD 25 + T细胞系在其生长中是肿瘤细胞依赖性的，但不裂解自体肿瘤细胞。该T细胞系抑制了同种异体淋巴细胞的美洲商陆有丝分裂原反应，建立的自体CTL的增殖活性，以及自体新鲜分离的外周血单核细胞中CTL的诱导。CD 4 +/CD 25+调节性T细胞的免疫抑制作用由转化生长因子β介导，不需要细胞与细胞接触。因此，尽管CRC患者可以发展针对其肿瘤的特异性CTL，但调节性T细胞的发展可能允许肿瘤细胞逃避体内CTL的免疫监视。
Cancer patients often develop CTLs that lyse autologous tumor cells in culture. However, tumors can progress in vivo despite the presence of CTLs. Various mechanisms have been reported to down-modulate CTL functions. In this study, the role of CD4+/CD25+ regulatory T cells in CTL induction and proliferation of established CTLs was investigated in a patient with CRC. CD4+ cytotoxic and regulatory T-cell lines were derived from the peripheral blood mononuclear cells of the same patient in mixed-lymphocyte tumor culture. The cytotoxic T-cell line and a clonal derivative specifically lysed the autologous tumor cells but not the B lymphocytes. Only HLA-A1-matched allogeneic CRC cells were lysed by the CTL clone. The clone produced IFN-gamma and TNF-alpha. The regulatory CD4+/CD25+ T-cell line was tumor cell-dependent in its growth but did not lyse autologous tumor cells. This T-cell line suppressed pokeweed mitogen responses of allogeneic lymphocytes, proliferative activity of the established, autologous CTLs, and induction of CTLs in autologous, freshly isolated peripheral blood mononuclear cells. The immunosuppressive effect of the CD4+/CD25+ regulatory T cells was mediated by transforming growth factor-beta and did not require cell-to-cell contact. Thus, although CRC patients can develop specific CTLs against their tumors, the development of regulatory T cells may allow the escape of tumor cells from immune surveillance by the CTLs in vivo.