CD4+ CD25+ regulatory T cells control the induction of antigen-specific CD4+ helper T cell responses in cancer patients

CD4+ CD25+ regulatory T cells control the induction of antigen-specific CD4+ helper T cell responses in cancer patients
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DOI:
10.1182/blood-2005-02-0607
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发表时间:
2005-08-01
期刊:
影响因子:
20.3
通讯作者:
Gnjatic, S
Gnjatic, S
中科院分区:
医学1区
文献类型:
--
作者:
Nishikawa, H;Jäger, E;Gnjatic, S

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部分癌症患者自然会对NY-ESO-1产生与抗NY-ESO-1血清抗体相关的CD4(+)T辅助细胞1型(Th1)细胞反应。为了探讨T细胞调节在控制自发肿瘤免疫中的作用,我们在体外分析了NY-ESO-1特异性Th1细胞在去除CD4(+)CD25(+)T细胞之前或之后的诱导。在NY-ESO-1血清阳性的癌症患者中,在CD25(+)T细胞存在的情况下产生Th1细胞,而血清阴性的癌症患者和健康献血者需要CD25(+)T细胞在体外诱导NY-ESO-1特异性Th1细胞。在体外,新产生的NY-ESO-1特异性Th1细胞来自幼稚的前体细胞,而先前存在的记忆群体仅在NY-ESO-1抗体阳性的患者中可检测到。记忆群体对CD4(+)CD25(+)调节性T细胞的敏感性低于幼稚群体。我们认为,CD4(+)CD25(+)调节性T细胞参与了NY-ESO-1特异性抗肿瘤免疫的产生和调节。
A proportion of cancer patients naturally develop CD4(+) T-helper type 1 (Th1) cell responses to NY-ESO-1 that correlate with anti-NY-ESO-1 serum antibodies. To address the role of T-cell regulation in the control of spontaneous tumor immunity, we analyzed NY-ESO-1-specific Th1 cell induction before or after depletion of CD4(+)CD25(+) T cells in vitro. While Th1 cells were generated in the presence of CD25(+) T cells in cancer patients seropositive for NY-ESO-1, seronegative cancer patients and healthy donors required CD25(+) T-cell depletion for in vitro induction of NY-ESO-1-specific Th1 cells. In vitro, newly generated NY-ESO-1-specific Th1 cells were derived from naive precursors, whereas preexisting memory populations were detectable exclusively in patients with NY-ESO-1 antibody. Memory populations were less sensitive than naive populations to CD4(+)CD25(+) regulatory T cells. We propose that CD4(+)CD25(+) regulatory T cells are involved in the generation and regulation of NY-ESO-1-specific antitumor immunity.