Tsunemi Sachi, Iwasaki Tsuyoshi, Imado Takehito, Higasa Satoshi, Kakishita Eizo, Shirasaka Takuma, Sano Hajime
Division of Thrombosis and Hemostasis, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
AIDS. 2005 Jun 10;19(9):879-86. doi: 10.1097/01.aids.0000171401.23243.56.
To determine whether the frequencies of CD4+CD25+ regulatory T cells (T Reg) were related to immune status in HIV-infected patients.
Peripheral blood CD4 T-cell populations were examined for T-helper 1 cells (Th1), T-helper 2 cells (Th2), and T Reg by intracellular staining for interferon (IFN)-gamma and interleukin (IL)-4, and surface staining for CD25, respectively. The immunoregulatory properties of T Reg were assessed by measurement of the inhibitory effects of isolated CD4+CD25+ T Reg on CD4+CD25- T-cell proliferation.
Isolated CD4+CD25+ T Reg from both HIV-infected patients and healthy controls strongly expressed CD45RO, HLA-DR, and FoxP3. HIV-infected patients with detectable plasma HIV-1 RNA showed a statistically significant increase in CD4+CD25high T Reg frequencies (P < 0.05) compared to healthy controls, with T Reg frequency inversely proportional to CD4 T-cell count (P < 0.01). However, in HIV-infected patients with undetectable plasma HIV-1 RNA, CD4+CD25high T Reg frequencies were not increased and were not related to CD4 T-cell counts. In both HIV-infected patient groups, T Reg frequency was inversely related to Th1 frequency (detectable HIV-1 RNA: P < 0.05; undetectable: P < 0.001), but positively related to Th2 frequency (detectable HIV-1 RNA: P < 0.01; undetectable: P < 0.001). T Reg activity was lower in patients with detectable plasma HIV-1 RNA than in patients with undetectable plasma HIV-1 RNA.
Increased T Reg frequencies in peripheral blood were related to low peripheral blood CD4 T-cell counts and polarization toward Th2 immune responses in HIV-infected patients.
确定CD4+CD25+调节性T细胞(T Reg)的频率是否与HIV感染患者的免疫状态相关。
通过对干扰素(IFN)-γ和白细胞介素(IL)-4进行细胞内染色,以及对CD25进行表面染色,分别检测外周血CD4 T细胞群体中的辅助性T细胞1(Th1)、辅助性T细胞2(Th2)和T Reg。通过测量分离出的CD4+CD25+ T Reg对CD4+CD25- T细胞增殖的抑制作用,评估T Reg的免疫调节特性。
从HIV感染患者和健康对照中分离出的CD4+CD25+ T Reg均强烈表达CD45RO、HLA-DR和FoxP3。与健康对照相比,血浆HIV-1 RNA可检测到的HIV感染患者的CD4+CD25high T Reg频率有统计学显著增加(P < 0.05),T Reg频率与CD4 T细胞计数呈负相关(P < 0.01)。然而,在血浆HIV-1 RNA不可检测的HIV感染患者中,CD4+CD25high T Reg频率未增加,且与CD4 T细胞计数无关。在两个HIV感染患者组中,T Reg频率与Th1频率呈负相关(可检测到HIV-1 RNA:P < 0.05;不可检测到:P < 0.001),但与Th2频率呈正相关(可检测到HIV-1 RNA:P < 0.01;不可检测到:P < 0.001)。血浆HIV-1 RNA可检测到的患者的T Reg活性低于血浆HIV-1 RNA不可检测到的患者。
外周血中T Reg频率增加与HIV感染患者外周血CD4 T细胞计数低以及向Th2免疫反应极化有关。