HAART reduces death ligand but not death receptors in lymphoid tissue of HIV-infected patients and simian immunodeficiency virus-infected macaques.
HAART reduces death ligand but not death receptors in lymphoid tissue of HIV-infected patients and simian immunodeficiency virus-infected macaques.
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DOI：
10.1097/qad.0b013e32831cb907
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发表时间：
2009-01-02
期刊：
影响因子：
--
通讯作者：
Shearer GM
中科院分区：
文献类型：
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作者：
Herbeuval JP;Nilsson J;Boasso A;Hardy AW;Vaccari M;Cecchinato V;Valeri V;Franchini G;Andersson J;Shearer GM
To determine how anti-retroviral therapy (ART/HAART) affects expression of apoptotic ligands and their death receptors in the blood and lymphoid tissues of HIV-infected patients and SIV-infected macaques. We analyzed mRNA expression of death molecules (TRAIL and FasL) and their receptors (DR5 and Fas) in blood and tonsils from HIV-infected patients (HIV+), HIV-infected patients receiving HAART (HAART) and HIV-uninfected (HIV−) donors in a cross-sectional study. We comparatively analyzed mRNA expression of TRAIL and DR5 in blood and lymph nodes collected longitudinally from SIV-infected macaques before and after ART. Expression of TRAIL, FasL, DR5 and Fas were elevated in circulating CD4+ T cells from a group of HIV+ patients, compared to both HIV− donors and HAART patients. In a different study group, TRAIL, FasL, DR5 and Fas were increased in tonsils of HIV+ patients compared to HIV− donors, and HAART patients. However, tonsils from HAART patients showed reduced expression of TRAIL and FasL but not DR5 and Fas, compared to HIV+ patients. Similarly, data obtained in longitudinal study of SIV-infected macaques showed that ART reduced both TRAIL and DR5 in peripheral blood, but only TRAIL and not DR5, in lymph nodes from the same animals. These findings suggest that HAART/ART is ineffective in reducing expression of apoptotic death receptors in lymphoid tissue. However, analysis limited to blood leukocytes may not reveal such a defect. Our results highlight the persistence of an underlying immunologic condition that may prevent therapy-induced restoration of CD4+ T cells in lymphoid tissue.
