LPS和R848对Tfh细胞表达Ki67和BcL6以及CXCR5的影响

Impact of LPS and R848 stimulating to Ki67, BcL6 and CXCR5 expression of T follicular helper cells

目的评估HIV感染及感染后微生物易位对滤泡辅助T淋巴细胞（T follicular helper cells，Tfh）功能的影响。方法选取HIV感染者外周浅表淋巴结（Lymph nodes，LNs），分离淋巴细胞，在存在或不存在HIV感染情况下，分别以脂多糖（lipopolysaccharide，LPS）和R848刺激；采用流式细胞术检测Tfh细胞表达Ki67、BcL6和CXCR5情况。结果LPS和R848刺激可促使Tfh细胞扩张并高表达BcL6，与LPS比，R848起效晚，但效果更强。虽然LPS可协助HIV抑制Tfh细胞表达BcL6，但HIV-1可能才是Tfh细胞下调BcL6表达的根本原因。此外，LPS和R848刺激可导致Tfh细胞下调CXCR5表达，使Tfh细胞接受CXCL13趋化定位的能力降低。 结论HIV感染是导致Tfh细胞功能异常的根本原因，但消化道微生物产物的漏入可能在感染后Tfh细胞功能异常中，起到了协同增效作用。因此，抑制感染后微生物产物易位，可能改善感染者体液免疫功能。

Objective To evaluate the possible impact of HIV infection and microbic products on the function of T follicular helper cells（Tfh）. Methods Lymph nodes of non-HIV infected individuals were recruited, and then ground gently and isolated into single lymphocytes. Ki67, BcL6 and CXCR5 expressions of Tfh were determined by flow cytometry after stimulation of lipopolysaccharide（LPS） and R848, or along with HIV-1 infection, respectively. Results The stimulation of LPS and R848 induced the expansion and BcL6 expression of Tfh. These effects of R848 started late but were stronger comparing to LPS. HIV-1 was intrinsic reason which downregulated the expression of BcL6 in Tfh, but LPS played a synergetie role in that. Moreover, the stimulation of LPS and R848 also downregulated the expression of CXCR5 in Tfh surface, which could impeded the ability of Tfh locating in lymphoid follicle. Conclusions HIV is the intrinsic reason which results in the abnormal function of Tfh, but the translocation of microbic products play a synergetic role. Therefore, inhibiting the translocation of microbic products could improve the adaptive immunity of host.