Sasson Sarah C, Zaunders John J, Zanetti Giulia, King Eleanor M, Merlin Kate M, Smith Don E, Stanley Keith K, Cooper David A, Kelleher Anthony D
National Centre in HIV Epidemiology and Clinical Research, Sydney, Australia.
J Infect Dis. 2006 Feb 15;193(4):505-14. doi: 10.1086/499309. Epub 2006 Jan 17.
Interleukin (IL)-7 levels are increased in patients with human immunodeficiency virus type 1 (HIV-1)-associated lymphopenia; however, the effects of this on IL-7 receptor (IL-7R) expression, disease progression, and immune reconstitution remain unclear.
Plasma IL-7 levels were measured, by enzyme-linked immunoassay, in patients with primary, chronic, or long-term nonprogressive HIV-1 infection (PHI, CHI, and LTNP, respectively) before and after 40-48 weeks of antiretroviral therapy (ART). Cell-surface expression and intracellular expression of the IL-7R components CD127 and CD132 were measured by flow cytometry. The effects of IL-7 and cycloheximide on IL-7R expression by peripheral blood mononuclear cells were examined in vitro.
Plasma IL-7 levels were increased in both patients with PHI and those with CHI; administration of ART resulted in normalized plasma IL-7 levels in patients with PHI but not in those with CHI. Plasma IL-7 levels positively correlated with CD4(+) T cell immune reconstitution in patients with PHI. In vitro, exogenous IL-7 rapidly down-regulated cell-surface CD127 expression, but not CD132 expression, whereas subsequent reexpression required active protein synthesis. HIV-1 infection resulted in progressive decreases in the CD127(+)132(-) subset and increases in the CD127(-)132(+) subset of CD4(+) and CD8(+) T cells. Changes in CD4(+) T cell expression of IL-7R components were evident in patients with LTNP who lost viral control, and these changes preceded increases in plasma IL-7 levels.
Perturbations in the IL-7/IL-7R system were clearly associated with disease progression but did not reliably predict immune reconstitution.
白细胞介素（IL）-7水平在1型人类免疫缺陷病毒（HIV-1）相关淋巴细胞减少症患者中升高；然而，其对IL-7受体（IL-7R）表达、疾病进展和免疫重建的影响仍不清楚。
通过酶联免疫吸附测定法测量原发性、慢性或长期非进展性HIV-1感染患者（分别为PHI、CHI和LTNP）在抗逆转录病毒治疗（ART）40 - 48周前后的血浆IL-7水平。通过流式细胞术测量IL-7R成分CD127和CD132的细胞表面表达和细胞内表达。在体外研究IL-7和环己酰亚胺对外周血单个核细胞IL-7R表达的影响。
PHI患者和CHI患者的血浆IL-7水平均升高；ART治疗使PHI患者的血浆IL-7水平恢复正常，但CHI患者未恢复。PHI患者的血浆IL-7水平与CD4(+) T细胞免疫重建呈正相关。在体外，外源性IL-7迅速下调细胞表面CD127表达，但不影响CD132表达，而随后的重新表达需要活性蛋白合成。HIV-1感染导致CD4(+)和CD8(+) T细胞的CD127(+)132(-)亚群逐渐减少，CD127(-)132(+)亚群增加。在失去病毒控制的LTNP患者中，CD4(+) T细胞IL-7R成分的表达变化明显，且这些变化先于血浆IL-7水平升高。
IL-7/IL-7R系统的紊乱与疾病进展明显相关，但不能可靠地预测免疫重建。
