Aguilar Patricia, Renoult Edith, Jarrosson Loraine, Kolopp-Sarda Marie Nathalie, Mathieu Christine Prin, Faure Gilbert C, Kessler Michele, Bene Marie C, Kohler Chantal, Kennel De March Anne
Laboratoire d'Immunologie du CHU, Faculté de Médecine, 54500 Vandoeuvre les Nancy, France.
Clin Diagn Lab Immunol. 2003 Nov;10(6):1117-22. doi: 10.1128/cdli.10.6.1117-1122.2003.
Patients with renal failure represent a population at risk for hepatitis B, since only 50 to 60% of them develop protective humoral responses after vaccination. As this could be due to an altered regulation of cellular immune responses, the objectives of the present study were to evaluate the proliferative abilities of lymphocytes from patients with chronic renal failure after stimulation in vitro with a mitogen (pokeweed mitogen [PWM]) or HBsAg. In order to differentiate between the immunodeficiency associated with renal failure and that due to immunosuppression posttransplantation, the same subjects were tested before and 4 months after kidney transplantation. The lymphoproliferation assay used was performed by flow cytometry, which is based on sequential analysis of the cell cycle and which allows analysis of cytokine production. Serologically, the group of 36 patients tested comprised 22% nonresponders, 30% poor responders, and 48% responders. Lymphocyte growth was observed for all patients after stimulation with PWM, indicating that these cells had the capacity to proliferate in vitro. The level of lymphoproliferation in response to PWM was significantly reduced after transplantation, yet both before and after transplantation, all serologic nonresponders developed cellular responses to at least two vaccines. No correlation between humoral and cellular responses was shown. Proliferating cells were lymphocytes, which mostly secreted interleukin 4 (IL-4) and IL-10 for the three serologic groups. This study suggests that even when repeated vaccination fails to induce significant antibody levels in patients with renal failure, specific HBs cellular responses develop, and these may prove to be efficient in protecting these patients against hepatitis B.
肾衰竭患者是感染乙型肝炎的高危人群,因为只有50%至60%的患者在接种疫苗后会产生保护性体液免疫反应。由于这可能是由于细胞免疫反应调节异常所致,本研究的目的是评估慢性肾衰竭患者的淋巴细胞在体外用丝裂原(商陆丝裂原[PWM])或乙肝表面抗原(HBsAg)刺激后的增殖能力。为了区分与肾衰竭相关的免疫缺陷和移植后免疫抑制导致的免疫缺陷,对同一组受试者在肾移植前和移植后4个月进行了检测。所采用的淋巴细胞增殖试验通过流式细胞术进行,该技术基于对细胞周期的顺序分析,并且能够分析细胞因子的产生。血清学检测方面,接受检测的36例患者中,22%为无反应者,30%为低反应者,48%为反应者。所有患者在用PWM刺激后均观察到淋巴细胞生长,表明这些细胞具有体外增殖能力。移植后对PWM的淋巴细胞增殖水平显著降低,但在移植前后,所有血清学无反应者对至少两种疫苗均产生了细胞免疫反应。体液免疫和细胞免疫反应之间未显示出相关性。增殖细胞为淋巴细胞,在三个血清学组中,这些细胞大多分泌白细胞介素4(IL-4)和白细胞介素10。本研究表明,即使反复接种疫苗未能在肾衰竭患者中诱导出显著的抗体水平,特异性乙肝细胞免疫反应仍会产生,并且这些反应可能对保护这些患者免受乙型肝炎感染有效。