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目的探讨白介素10(IL-10)受体阻断剂(Anti-IL-10R)或/和外源性IL-15(单独或联合)对HIV-1感染者T淋巴细胞增殖的影响。方法纳入50例HIV-1感染者作为研究对象,接受抗病毒治疗组(HAART组)及未接受抗病毒治疗组(HAART-na?ve组)病例分别为27例及23例。以HIV-1 P24编码区的氨基酸序列人工合成的13个肽段组成的肽段库作为特异性抗原刺激表位,采用羧乙基锗倍半氧化物(CFSE)对外周血单个核细胞(PBMC)示踪染色,在Anti-IL-10R及外源性IL-15(单独或联合)存在条件下,与PBMC共培养,流式细胞仪检测T淋巴细胞增殖情况。结果 HAART组及HAART-na?ve组,Anti-IL-10R、IL-15、Anti-IL-10R/IL-15刺激孔的CD4~+及CD8~+T的中位增殖倍数分别与对照孔比较,CD4~+T细胞的结果分别为:0.98(P=0.45),1.06(P=0.18);1.24(P=0.006),1.27(P=0.06);1.05(P=0.314),1.08(0.003),CD8~+T细胞增殖倍数分别为:0.94(P=0.45),1.17(P=0.177);1.96(P=0.000),1.37(P=0.000);1.49(P=0.000),1.34(P=0.000)。在HAART组中,CD4~+T细胞增殖与Anti-IL-10R相关(r_s=0.195,P=0.021),CD8~+T细胞增殖与IL-15相关(r_s=0.717,P<0.0001)。在HAART-na?ve组中,CD4~+及CD8~+T细胞增殖均与IL-15相关(r_s=0.341,P=0.003;r_s=0.876,P<0.0001)。无论HAART组还是HAART-na?ve组,CD4~+T细胞和CD8~+T细胞增殖与CD4、CD8、Th/Ts及HIV-1病毒载量均无明显相关性。结论外源性IL-15能促进HIV-1感染者T淋巴细胞体外增殖,并且经HAART治疗后这一作用似乎更强;IL-10R阻断剂可能对HIV-1感染者的CD4~+T淋巴细胞有潜在的体外促活化及增殖作用。
Objective To investigate the effects of interleukin-10 (IL-10) receptor blocker (IL-10) receptor antagonist and / or exogenous IL-15 (alone or in combination) on T lymphocyte proliferation in HIV-1 infected patients. Methods Fifty HIV-1 infected individuals were enrolled in this study. Twenty-seven and 23 HAART-naïve patients were treated with antiviral therapy (HAART) and antiviral therapy (HAART-naïve) respectively. Peptide library consisting of 13 peptides synthesized by the amino acid sequence of the HIV-1 P24 coding region was used as a specific antigen-stimulating epitope. Peripheral blood mononuclear cells (PBMCs) were stained with carboxyethyl germanium sesquioxide (CFSE) ) Tracing staining, co-cultured with PBMC in the presence of Anti-IL-10R and exogenous IL-15 (alone or in combination), and the proliferation of T lymphocytes was detected by flow cytometry. Results The median multiplication of CD4 ~ + and CD8 ~ + T in HAART group and HAART-na? Ve group, Anti-IL-10R, IL-15 and Anti-IL-10R / IL- The results of CD4 ~ + T cells were 0.98 (P = 0.45), 1.06 (P = 0.18), 1.04 ) And CD8 ~ + T cell proliferation were 0.94 (P = 0.45), 1.17 (P = 0.177), 1.96 (P = 0.000), 1.37 = 0.000). In the HAART group, the proliferation of CD4 ~ + T cells was correlated with Anti-IL-10R (r_s = 0.195, P = 0.021), while the proliferation of CD8 + T cells was correlated with IL-15 (r_s = 0.717, P <0.0001). In the HAART-na? Ve group, both CD4 ~ + and CD8 ~ + T cell proliferation correlated with IL-15 (r_s = 0.341, P = 0.003; r_s = 0.876, P <0.0001). The proliferation of CD4 ~ + T cells and CD8 ~ + T cells had no significant correlation with CD4, CD8, Th / Ts and HIV-1 viral load in HAART group and HAART-na? Ve group. Conclusion Exogenous IL-15 can promote the proliferation of T lymphocytes in HIV-1 infected patients in vitro, and this effect seems to be stronger after treatment with HAART. IL-10R blocker may inhibit CD4 ~ + T Lymphocytes have potential in vitro activation and proliferation.