同胞HLA全相合骨髓和外周血造血干细胞混合移植后血液病患者CMV特异性T细胞免疫重建规律

Cytomegalovirus-specific T cells immune reconstitution after human leukocyte antigen matched sibling donor aliogeneic bone marrow plus peripheral blood hematopoietic stem cell transplantation

目的探讨同胞人类白细胞抗原（HLA）全相合骨髓和外周血造血干细胞混合移植（allo—HSCT）后CMV特异性细胞毒性T细胞（CTL）的重建规律。方法选取17例接受allo—HSCT的血液病患者，采用流式细胞术检测移植后CMV特异性CTL及其亚群数量，酶联免疫斑点（ELISPOT）法检测重建CTL分泌IFN一^y的功能，采用基因扫描方法对移植后受者TCRv[3亚家族进行克隆性分析，并研究CTL重建与CMV感染的关系。结果移植受者CMV特异性CTL数量和功能均可在移植后30d重建至正常对照水平，并且在移植后12个月TCRVB亚家族已大部分呈多克隆表现。随访期间该组患者移植后CMV感染发生率为35．83％（17．91％～63．10％），均未发生CMV病，当发生CMV感染时外周血CMV特异性CTL中枢记忆T细胞（CD45RO’CD62L’）亚群数量明显增多。结论血液病患者接受同胞HIJA相合骨髓和外周血造血干细胞混合移植后，其CMV特异性CTL数量及功能均能早期重建，CMV感染和CMV病发生率较低。

Objective To investigate the regular pattern of Cytomegalovirus （CMV）-specific T cells （CTL） immune reconstitution after human leukocyte antigen （HLA） matched sibling donor allogeneic bone marrow （ BM ） plus peripheral blood bematopoietic stem cell （ PBSC ） transplantation. Methods CTL from seventeen patients after transplantation was detected by flow cytometry, the IFN-~ secretion ability of CTL by enzyme - linked immunospot（ELISPOT） assay, and clonal analysis of TCR VII subfamily by gene scan as- says. The relationship between CTL reconstitution and CMV infection was studied. Results Both number and function of recipients CTL reached to normal control level at 30 d post-transplantation. The recipients achieved a high frequency CTL with IFN-~/response and restoration of T-cell receptor 13 （ TCR V13） repertoire at one year post-transplantation. CTL with the central memory CD45RO ＋ CD62L ＋ cell phenotype expanded in PB when CMV was reactivated. The incidence of CMV reactivation was 35.83% （ 17.91% -63.10% ） after transplantation, and none of them developed CMV disease. Conclusion After HLA matched related donor transplantation using mixed grafts, immune recovery to CMV seems to be early and fast. The incidence of CMV infection and disease are lower.