Impaired Immune Responses and Antigen-Specific Memory CD4+ T Cells in Hemodialysis Patients
Impaired Immune Responses and Antigen-Specific Memory CD4+ T Cells in Hemodialysis Patients
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DOI：
10.1681/asn.2007090971
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发表时间：
2008-08-01
影响因子：
13.6
通讯作者：
Betjes, Michiel Gerardus Henricus
中科院分区：
文献类型：
--
作者：
Litjens, Nicolle Helena Renier;Huisman, Martin;Betjes, Michiel Gerardus Henricus
终末期肾病患者对T细胞依赖性疫苗接种的血清学应答严重减弱，但其原因尚不清楚。在这项研究中，进行了抗原特异性T细胞应答的详细分析。血液透析患者和年龄和性别匹配的健康对照受试者接种了B型肝炎表面抗原（HBsAg），定期用细胞内细胞因子染色和增殖试验监测抗原特异性CD 4（+）T细胞。使用针对CD 45 RO和趋化因子受体CCR 7的抗体将产生IL-2和IFN-γ的CD 4（+）T细胞鉴定为中枢或效应记忆CD 4（+）T细胞。对照受试者出现记忆T细胞反应，包括中枢记忆CD 4（+）T细胞和效应记忆CD 4（+）T细胞，其中中枢记忆反应发生在效应记忆反应之前1周。IL-2（+）Ag特异性记忆性CD 4（+）T细胞主要在效应细胞群中检测到。终末期肾病患者表现出产生IL-2和IFN-γ的中枢记忆性CD 4（+）T细胞的延迟反应，但其最大反应与对照组相似。相比之下，ESRD患者产生的IL-2（+）HBsAg特异性效应记忆CD 4（+）T细胞仅为对照组的6.3%（0.5 +/- 0.2 x 10（4）/L vs 8 +/- 3.5 x 10（4）/L; P < 0.001），这种受损的反应与抗原特异性T细胞增殖和抗HBsAg IgG滴度相关。总之，疫苗接种后抗原特异性效应记忆CD 4（+）T细胞的产生，这是实现足够的体液应答的关键，在ESRD患者中严重受损。
Serologic responses to T cell-dependent vaccinations are severely attenuated in patients with ESRD, but the reasons for this is unknown. In this study, a detailed analysis of antigen-specific T cell responses was performed. Patients on hemodialysis and age- and gender-matched healthy control subjects were vaccinated with hepatitis B surface antigen (HBsAg), antigen-specific CD4(+) T cells were monitored at regular intervals with intracellular cytokine staining and proliferation assays. IL-2- and IFN-gamma-producing CD4(+) T cells were identified as either central or effector memory CD4(+) T cells using antibodies directed against CD45RO and the chemokine receptor CCR7. Control subjects mounted a memory T cell response comprising both central and effector memory CD4(+) T cells, with the central memory response occurring 1 wk before the effector memory response. IL-2(+) HBsAg-specific memory CD4(+) T cells were primarily detected within the effector population. Patients with ESRD showed a delayed response of IL-2- and IFN-gamma-producing central memory CD4(+) T cells, but their maximal responses were similar to those of control subjects. In contrast, patients with ESRD produced only 6.3% of the IL-2(+) HBsAg-specific effector memory CD4(+) T cells produced by control subjects (0.5 +/- 0.2 x 10(4)/L versus 8 +/- 3.5 x 10(4)/L; P < 0.001), and this impaired response correlated with antigen-specific T cell proliferation and anti-HBsAg IgG titers. In conclusion, the production of antigen-specific effector memory CD4(+) T cells after vaccination, which is critical to achieve an adequate humoral response, is severely impaired in patients with ESRD.