尽管T辅助细胞反应无效,但在自体造血干细胞移植受者中仍存在完全免疫活性的CD8 + T淋巴细胞。

Fully immunocompetent CD8+ T lymphocytes are present in autologous haematopoietic stem cell transplantation recipients despite an ineffectual T-helper response.

作者信息

Bandera Alessandra, Trabattoni Daria, Pacei Michela, Fasano Francesca, Suardi Elisa, Cesari Miriam, Marchetti Giulia, Pogliani Enrico M, Franzetti Fabio, Clerici Mario, Gori Andrea

机构信息

Division of Infectious Diseases, Department of Internal Medicine, "San Gerardo" Hospital, University of Milan-Bicocca, Monza, Italy.

出版信息

PLoS One. 2008;3(10):e3616. doi: 10.1371/journal.pone.0003616. Epub 2008 Oct 31.

Abstract

BACKGROUND

Reduced CD4 T lymphocytes counts can be observed in HIV infection and in patients undergoing autologous haematopoietic stem cell transplantation (ASCT). Nevertheless, whereas opportunistic infections (OI) are frequent in HIV-infected individuals with low cell counts, OI are uncommon in ASCT patients.

METHODOLOGY/PRINCIPAL FINDINGS: To verify whether this observation could be secondary to intrinsic HIV-correlated T cell defects, we performed in-depth immunologic analyses in 10 patients with comparable CD4 counts in whom lymphopenia was secondary either to HIV-infection or ASCT-associated immunosuppressive therapy and compared them to age-matched healthy subjects. Results showed the presence of profound alterations in CD4+ T lymphocytes in both groups of patients with respect to healthy controls. Thus, a low percentage of CCR7+ CD4+ T cells and a compensative expansion of CD45RA-CCR7- CD4+ T cells, a reduced IL-2/IFN-gamma cytokine production and impaired recall antigens-specific proliferative responses were detected both in ASCT and HIV patients. In stark contrast, profound differences were detected in CD8+ T-cells between the two groups of patients. Thus, mature CD8+ T cell prevailed in ASCT patients in whom significantly lower CD45RA-CCR7- cells, higher CD45RA+CCR7- CD8+ cells, and an expansion of CCR7+CD8+ cells was detected; this resulted in higher IFN-gamma +/TNFalpha production and granzyme CD8+ expression. The presence of strong CD8 T cells mediated immune responses justifies the more favorable clinical outcome of ASCT compared to HIV patients.

CONCLUSION/SIGNIFICANCE: These results indicate that CD8 T cells maturation and functions can be observed even in the face of a profound impairment of CD4+ T lymphocytes in ASCT but not in HIV patients. Primary HIV-associated CD8 defects or an imprinting by an intact CD4 T cell system in ASCT could justify these results.

摘要

背景

在HIV感染患者以及接受自体造血干细胞移植(ASCT)的患者中均可观察到CD4 T淋巴细胞计数减少。然而,尽管CD4细胞计数低的HIV感染者中机会性感染(OI)很常见,但OI在ASCT患者中并不常见。

方法/主要发现:为了验证这一观察结果是否可能继发于与HIV相关的内在T细胞缺陷,我们对10例CD4计数相当的患者进行了深入的免疫学分析,这些患者的淋巴细胞减少继发于HIV感染或ASCT相关的免疫抑制治疗,并将他们与年龄匹配的健康受试者进行比较。结果显示,与健康对照组相比,两组患者的CD4+ T淋巴细胞均存在深刻改变。因此,在ASCT患者和HIV患者中均检测到CCR7+ CD4+ T细胞百分比低,CD45RA-CCR7- CD4+ T细胞代偿性扩增,IL-2/IFN-γ细胞因子产生减少以及回忆抗原特异性增殖反应受损。形成鲜明对比的是,两组患者的CD8+ T细胞存在显著差异。因此,成熟的CD8+ T细胞在ASCT患者中占优势,在这些患者中检测到CD45RA-CCR7-细胞显著减少,CD45RA+CCR7- CD8+细胞增多,以及CCR7+CD8+细胞扩增;这导致更高的IFN-γ +/TNFα产生和颗粒酶CD8+表达。强大的CD8 T细胞介导的免疫反应的存在证明了ASCT患者与HIV患者相比具有更有利的临床结果。

结论/意义:这些结果表明,即使在ASCT患者中CD4+ T淋巴细胞严重受损的情况下也可观察到CD8 T细胞的成熟和功能,但在HIV患者中则不然。原发性HIV相关的CD8缺陷或ASCT中完整CD4 T细胞系统的印记可以解释这些结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e505/2570790/3b2775148d9e/pone.0003616.g001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索