Perforin is not co-expressed with granzyme A within cytotoxic granules in CD8 T lymphocytes present in lymphoid tissue during chronic HIV infection
Perforin is not co-expressed with granzyme A within cytotoxic granules in CD8 T lymphocytes present in lymphoid tissue during chronic HIV infection
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DOI：
10.1097/00002030-199907300-00005
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发表时间：
1999-07-30
期刊：
影响因子：
3.8
通讯作者：
Fehniger, TE
中科院分区：
文献类型：
--
作者：
Andersson, J;Behbahani, H;Fehniger, TE
背景资料：尽管进行了抗逆转录病毒治疗，但通过效应细胞毒性T淋巴细胞（eCTL）从淋巴组织（LT）储库中消除残留的HIV-1感染细胞的能力很差。穿孔素（Perforin）和颗粒酶A（grA）是eCTL颗粒内的主要效应分子，它们可诱导病毒感染细胞的凋亡和裂解。目的：在单细胞水平上研究16例HIV-1感染者LT和血液中穿孔素和grA的表达（A1-C期）未接受抗逆转录病毒治疗的患者。方法：通过对来自血液和LT的细胞进行原位成像的免疫组织化学分析。定量原位成像显示，表达穿孔素的CD 8 T细胞占最近HIV-1血清转换者LT内总细胞的0.3-1.5%，而grA占总细胞的2.1-7.2%。然而，尽管与未感染个体（0.4-0.9%）相比，grA高水平上调（占总细胞的1.5-4.5%），但慢性HIV-1感染患者（A2-C期）的LT中穿孔素表达仍然较低（<总细胞的0.1%）（P < 0.02）。这与来自同一HIV-1感染队列的外周血单核细胞（PBMC）中的发现形成对比，其中在所有PBMC中的13-31%中检测到穿孔素，其比淋巴组织中高10- 100倍（P < 0.001）;在总PBMC中的14-32%中发现grA。双色染色结果表明，穿孔素和grA的颗粒表达仅限于CD 8 T细胞在LT和blood.Conclusions总细胞的90%以上：这些研究结果表明，细胞毒性穿孔素的表达受损的HIV复制在淋巴组织内的局部网站。由于穿孔素与grA一起用于颗粒介导的细胞溶解，因此LT中穿孔素的低表达可能会限制eCTL消除淋巴组织中HIV-1感染细胞的能力。(C)1999年利平科特威廉姆斯&威尔金斯。
Background: Residual HIV-l-infected cells are poorly eliminated from lymphoid tissue (LT) reservoirs by effector cytotoxic T lymphocytes (eCTL) despite antiretroviral therapy. Perforin and granzyme A (grA) constitute major effector molecules within eCTL granules that induce apoptosis and lysis of virally infected cells.Objective: Expression of perforin and grA was studied at the single cell level in LT and blood from 16 patients infected with HIV-1 (stage A1-C) who were not taking antiretroviral therapy.Method: Immunohistochemical analysis by in situ imaging of cells from blood and LT.Results: Quantitative in situ imaging showed that perforin-expressing CD8 T cells comprised 0.3-1.5% of total cells within the LT from recent HIV-1 seroconverters, while grA was found in 2.1-7.2% of total cells. However, despite high-level grA upregulation (1.5-4.5% of total cells) compared with that in non-infected individuals (0.4-0.9%), perforin expression remained low (< 0.1% of total cells) (P < 0.02) in LT from patients with chronic HIV-1 infection (stage A2-C). This contrasted with findings in peripheral blood mononuclear cells (PBMC) from the same HIV-1 infected cohort where perforin was detected in 13-31% of all PBMC, which was 10- to 100-fold higher than in lymphoid tissue (P < 0.001); grA was found in 14-32% of total PBMC. Two-colour staining showed that granular expression of perforin and grA was restricted to CD8 T cells in over 90% of total cells in both LT and blood.Conclusions: These findings indicate that cytotoxic perforin expression is impaired at local sites of HIV replication within lymphoid tissue. Since perforin is required together with grA for granule-mediated cytolysis, the low perforin expression in the LT may limit the ability of eCTL to eliminate HIV-1 infected cells in lymphoid tissue. (C) 1999 Lippincott Williams & Wilkins.