T淋巴细胞活化在严重发热伴血小板减少综合征疾病发展中的作用

Role of T lymphocyte activation in the development of severe fever accompanied by thrombocytopenia syndrome

目的探讨严重发热伴血小板减少综合征病毒(SFTSV)感染过程中,外周血T淋巴细胞活化对血液细胞、组织损伤和疾病发展的影响。方法应用流式细胞术,动态定量监测严重发热伴血小板减少综合征(SFTS)患者外周血中T淋巴细胞表面CD69、HLA-DR、CD28和CTLA-4等表达水平,分析其细胞表面分子变化与血清酶学以及白细胞和血小板异常的关系。结果 SFTS患者T细胞活化分子CD69和HLA-DR在整个病程中表达水平明显增加(P<0.05);CD4+细胞表面CD28的表达在SFTSV感染早期明显减低,但随病程发展而逐渐回升至正常范围,而T细胞表面CTLA-4的高表达则出现在感染后的中晚期。SFTS患者病程中,血清ALT、AST和LDH、CK等均明显高于正常范围,并伴随着T细胞表面CD69、HLA-DR等活化分子下调和CTLA-4表达水平上调而逐步恢复正常;白细胞和血小板计数的最低值出现在病程初期,伴随着T细胞表面CD69、HLA-DR等活化分子下调和CTLA-4表达增加逐渐回升至正常范围。结论 T淋巴细胞的过度活化可能是组织损伤的主要因素之一,而CTLA-4高表达,则可能是对机体T淋巴细胞过度活化的一种负反馈调节,在SFSTV感染者的免疫应答调节中发挥重要作用。

Objective To explore the effect of peripheral blood T lymphocyte activation on the blood cells, tissue injury and the development of disease in patients with severe fever with thrombocytopenia syndrome （SFTS）. Methods The expressions of CD69, HI_A-DR, CD28 and CTLA-4 on peripheral blood T lymphocytes were determined dynamically by flow cytometry and the relationships between the above immune molecules and ALT, AST, leukocytes, platelets were analyzed respectively. Results The expressions of CD69 and HLA-DR on peripheral blood T lymphocytes in patients with SFTS were elevated signifi- cantly during the whole course of disease （ P 〈 0.05）. CD28 expression on CD4＋ lymphocyte subset decreased in the early stage and gradually increased to the normal range. Meanwhile, CTLA-4 expression on T lymphocytes went up in the late stage of viral infection. The levels of serum ALT, AST, LDH and CK were significantly higher than the upper limit of the nor- mal and the counts of WBC and PLT dropped to the lowest at the outset. But all of them returned back to the normal range gradually with the down-regulation of CD69 and HLA-DR and the up-regulation of CTLA-4 on T lymphocyte. Conclusion The overactivation of T lymphocytes may contribute to tissue injury and the high expression of CTLA-4 may be a negative feed- back regulation to the overactivation of T lymphocytes, which plays an important role in immunoregulation of SFTS patients.