Toulza Frederic, Nosaka Kisato, Takiguchi Masafumi, Pagliuca Tony, Mitsuya Hiroaki, Tanaka Yuetsu, Taylor Graham P, Bangham Charles R M
Department of Immunology, Imperial College, London, United Kingdom.
Int J Cancer. 2009 Nov 15;125(10):2375-82. doi: 10.1002/ijc.24664.
Human T-lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATLL). It has been postulated that ATLL cells might act as regulatory T cells (T(regs)) which, in common with ATLL cells, express both CD25 and FoxP3, and so contribute to the severe immune suppression typical of ATLL. We report here that the frequency of CD25(+) cells varied independently of the frequency of FoxP3(+) cells in both a cross-sectional study and in a longitudinal study of 2 patients with chronic ATLL. Furthermore, the capacity of ATLL cells to suppress proliferation of heterologous CD4(+)CD25(-) cells correlated with the frequency of CD4(+) FoxP3(+) cells but was independent of CD25 expression. Finally, the frequency of CD4(+)FoxP3(+) cells was inversely correlated with the lytic activity of HTLV-1-specific CTLs in patients with ATLL. We conclude that ATLL is not a tumor of FoxP3(+) regulatory T cells, and that a population of FoxP3(+) cells distinct from ATLL cells has regulatory functions and may impair the cell-mediated immune response to HTLV-1 in patients with ATLL.
人类嗜T淋巴细胞病毒1型（HTLV-1）是成人T细胞白血病/淋巴瘤（ATLL）的病原体。据推测，ATLL细胞可能充当调节性T细胞（Tregs），与ATLL细胞一样，表达CD25和FoxP3，从而导致ATLL典型的严重免疫抑制。我们在此报告，在一项横断面研究以及对2例慢性ATLL患者的纵向研究中，CD25(+)细胞的频率与FoxP3(+)细胞的频率独立变化。此外，ATLL细胞抑制异源CD4(+)CD25(-)细胞增殖的能力与CD4(+) FoxP3(+)细胞的频率相关，但与CD25表达无关。最后，ATLL患者中CD4(+)FoxP3(+)细胞的频率与HTLV-1特异性CTL的裂解活性呈负相关。我们得出结论，ATLL不是FoxP3(+)调节性T细胞的肿瘤，并且与ATLL细胞不同的FoxP3(+)细胞群体具有调节功能，可能会损害ATLL患者对HTLV-1的细胞介导免疫反应。
