Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France.
Blood. 2010 May 6;115(18):3708-17. doi: 10.1182/blood-2009-02-202796. Epub 2009 Dec 28.
Idiopathic CD4(+) T-cell lymphocytopenia (ICL) is a rare acquired T-cell immunodeficiency of unknown pathogenic basis. Six adults with ICL who developed opportunistic infections were investigated using extensive immunophenotyping analysis and functional evaluation of the chemokine receptor CXCR4. For all 6 patients studied, a profound defect in CXCR4 expression was detected at the surface of CD4(+) T lymphocytes, in association with an abnormal intracellular accumulation of CXCR4 and of its natural ligand, the chemokine CXCL12. For all patients studied, CD4(+) T-cell chemotactic response toward CXCL12 was decreased, whereas sensitivity to CXCL8 was preserved. CXCR4 recovery after ligand-induced endocytosis was impaired in ICL CD4(+) T cells. Upon in vitro addition of interleukin-2 (IL-2), membrane expression of CXCR4 returned to normal levels in 5 of 6 patients, whereas intracellular accumulation of CXCR4 and CXCL12 disappeared. Upon therapeutic administration of IL-2, CD4(+) T-cell count and membrane CXCR4 expression and function improved over time in 3 of 4 patients treated. Therefore, our data indicate that ICL is associated with defective surface expression of CXCR4, which may be reversed by IL-2.
特发性 CD4(+) T 细胞淋巴细胞减少症（ICL）是一种罕见的获得性 T 细胞免疫缺陷，其发病机制尚不清楚。对 6 例发生机会性感染的 ICL 成年人进行了广泛的免疫表型分析和趋化因子受体 CXCR4 的功能评估。对所有 6 例研究患者，均检测到 CD4(+) T 淋巴细胞表面 CXCR4 表达严重缺陷，同时存在 CXCR4 及其天然配体趋化因子 CXCL12 的异常细胞内积累。所有研究患者的 CD4(+) T 细胞对 CXCL12 的趋化反应均降低，而对 CXCL8 的敏感性保持不变。ICL CD4(+) T 细胞的 CXCR4 在配体诱导的内吞作用后的恢复受损。体外添加白细胞介素-2 (IL-2) 后，6 例患者中的 5 例 CXCR4 的膜表达恢复正常水平，而 CXCR4 和 CXCL12 的细胞内积累消失。在 IL-2 的治疗给药中，4 例接受治疗的患者中的 3 例随着时间的推移，CD4(+) T 细胞计数和膜 CXCR4 表达和功能得到改善。因此，我们的数据表明，ICL 与 CXCR4 的表面表达缺陷有关，IL-2 可能逆转这种缺陷。
