Damås J K, Landrø L, Fevang B, Heggelund L, Tjønnfjord G E, Fløisand Y, Halvorsen B, Frøland S S, Aukrust P
Research Institute for Internal Medicine, University of Oslo, Oslo, Norway.
Clin Exp Immunol. 2009 Sep;157(3):400-7. doi: 10.1111/j.1365-2249.2009.03976.x.
CCL19 and CCL21 and their receptor CCR7 are expressed constitutively within lymphoid organs, regulating lymphocyte homing. Recent studies suggest that these chemokines may have inflammatory properties. We hypothesized a role of CCL19/CCL21 in human immunodeficiency virus (HIV) infection by promoting inflammation. We examined the expression of CCL19 and CCL21 in mononuclear cells from peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) in HIV-infected patients before and during highly active anti-retroviral therapy (HAART). We also examined the ability of CCL19/CCL21 to promote inflammatory responses in these patients. PBMC from untreated HIV-infected patients (n = 29) released enhanced levels of CCL19 spontaneously compared with cells from controls (n = 20), particularly in those with symptomatic disease (n = 15, P < 0.01 versus controls). During HAART (n = 9), there was a decrease in the spontaneous CCL19 release and an increase in the phytohaemagglutinin-stimulated CCL19 release in both PBMC (P < 0.01) and BMMC (P < 0.05). In patients with enhanced HIV replication there was an increased proportion of inflammatory CD8(+)CCR7(-)CD45RA(-) T cells in peripheral blood [P < 0.01 and P < 0.05 versus controls, untreated (n = 9) and treatment failure (n = 8), respectively]. In vitro, CCL19/CCL21 promoted an inflammatory response in PBMC when accompanied by high viral load, irrespective of HAART. The HIV-tat protein significantly boosted the inflammatory effect of CCL19/CCL21 in PBMC. These findings link a dysregulated CCL19/CCL21/CCR7 system in HIV-infected patients to persistent inflammation and HIV replication, not only in untreated HIV infection, but also in treatment failure during HAART.
CCL19和CCL21及其受体CCR7在淋巴器官中持续表达，调节淋巴细胞归巢。最近的研究表明，这些趋化因子可能具有炎症特性。我们推测CCL19/CCL21通过促进炎症在人类免疫缺陷病毒（HIV）感染中发挥作用。我们检测了高效抗逆转录病毒治疗（HAART）前及治疗期间，HIV感染患者外周血单个核细胞（PBMC）和骨髓单个核细胞（BMMC）中CCL19和CCL21的表达。我们还检测了CCL19/CCL21促进这些患者炎症反应的能力。与对照组（n = 20）的细胞相比，未经治疗的HIV感染患者（n = 29）的PBMC自发释放的CCL19水平更高，尤其是有症状疾病的患者（n = 15，与对照组相比P < 0.01）。在HAART期间（n = 9），PBMC（P < 0.01）和BMMC（P < 0.05）中自发CCL19释放减少，而植物血凝素刺激的CCL19释放增加。在HIV复制增强的患者外周血中，炎症性CD8(+)CCR7(-)CD45RA(-) T细胞比例增加[与对照组、未经治疗的患者（n = 9）和治疗失败的患者（n = 8）相比，分别为P < 0.01和P < 0.05]。在体外，无论是否进行HAART，当病毒载量高时，CCL19/CCL21都会促进PBMC中的炎症反应。HIV-tat蛋白显著增强了CCL19/CCL21在PBMC中的炎症作用。这些发现表明，HIV感染患者中失调的CCL19/CCL21/CCR7系统与持续炎症和HIV复制有关，不仅在未经治疗的HIV感染中如此，在HAART治疗失败时也是如此。
