Adoptive transfer of costimulated CD4+ T cells induces expansion of peripheral T cells and decreased CCR5 expression in HIV infection
Adoptive transfer of costimulated CD4+ T cells induces expansion of peripheral T cells and decreased CCR5 expression in HIV infection
复制标题
DOI：
10.1038/nm0102-47
复制
发表时间：
2002-01-01
期刊：
影响因子：
82.9
通讯作者：
June, CH
中科院分区：
文献类型：
--
作者：
Levine, BL;Bernstein, WB;June, CH
为了研究T细胞重组在hiv感染者体内的安全性和可行性，我们过继性地转移了活化的自体CD4(+) T细胞。体外共刺激多克隆外周血CD4（+）细胞，并给受试者输注多达3 × 10（10）个活化的CD4（+）细胞。观察到CD4（+）细胞计数和CD4:CD8比值呈剂量依赖性增加。体内细胞因子分泌T细胞的比例持续增加，CD4(+)CCR5（+）细胞的比例下降，表明功能增强和对HIV感染的抵抗力。CD4(+)Ki-67（+）细胞的频率增加，而含有T细胞受体重排切除圈（trec）的CD4(+) T细胞的频率减少。这些发现表明外周t细胞池的扩大介导了CD4计数的增加，并表明重建CD4辅助细胞活性和降低CCR5表达的方法可能增强对HIV感染的天然免疫力。
To study the safety and feasibility of T-cell reconstitution in HIV-infected individuals, we adoptively transferred activated autologous CD4(+) T cells. Polyclonal peripheral blood CD4(+) cells were costimulated ex vivo and subjects were given infusions of up to 3 x 10(10) activated CD4(+) Cells. Dose-dependent increases in CD4(+) cell counts and in the CD4:CD8 ratio were observed. Sustained increases in the fraction of cytokine-secreting T cells and decreases in the percentage of CD4(+)CCR5(+) cells were noted in vivo, suggesting enhanced function and resistance to HIV infection. The frequency of CD4(+)Ki-67(+) cells increased whereas CD4(+) T cells containing T cell-receptor rearrangement excision circles (TRECs) decreased. These findings indicate that expansion of the peripheral T-cell pool mediated the increase in CD4 counts and suggest that approaches to reconstitute CD4 helper cell activity and decrease CCR5 expression may augment natural immunity to HIV infection.