Shenoy S, Mohanakumar T, Todd G, Westhoff W, Dunnigan K, Adkins D R, Brown R A, DiPersio J F
Department of Pediatric Hematology-Oncology (Division), St Louis Children's Hospital, Washington University School of Medicine, MO 63110, USA.
Bone Marrow Transplant. 1999 Feb;23(4):335-46. doi: 10.1038/sj.bmt.1701581.
Growth factor-mobilized peripheral blood stem cells (PBSCs) engraft rapidly in myeloablated recipients compared to conventional BM, but this procedure also mobilizes mature lymphocytes and monocytes which can impact immune reconstitution and GVHD. Hence, we serially evaluated immune reconstitution and cytokine expression in PBSCT recipients in the first year. Engraftment of neutrophils and monocytes stabilized early but NK cells, B cells and CD4+ T cell numbers were significantly (P < 0.05) low with persistently reversed CD4:CD8 ratios. NK function remained low throughout the first year. The quantitative decrease in CD4+ T cells resulted in significantly decreased proliferation in response to mitogens and alloHLA antigens. Yet, a qualitative analysis of T cell function measured by Ca++ influx after T cell activation with antiCD3 as well as T-dependent polyclonal Ig secretion by mitogen-stimulated B cells was preserved even early post transplant. TNF alpha mRNA was detected in almost all recipients in the first year. IL-10 mRNA was detected in 77%, IL-2 in 22% and IFN gamma in 44% of recipients in the first 6 months. Only 30% expressed IL-10 in the second 6 months post transplant while expression of IL-2 and IFN gamma was detected in 38% and 46% respectively. Thirty-seven percent of PBSCT recipients developed grades II-IV acute GVHD but 72% went on to develop chronic extensive GVHD at a median of 120 days. Sixty-two percent developed CMV viremia and 5.4% developed overt CMV disease in the first year post PBSCT. Lymphocyte engraftment is quantitatively delayed but CD4 functions are preserved while NK numbers and function are compromised post PBSCT. IL-10 expression decreases after the first 6 months post transplant while TNF alpha is continually expressed. The balance between quantitative lymphocyte reconstitution and qualitative lymphocyte functions as well as changes in lymphokine patterns may influence infection and GVHD and thus the clinical outcome post PBSCT.
与传统骨髓相比，生长因子动员的外周血干细胞（PBSCs）在接受清髓性预处理的受者体内植入迅速，但该过程也会动员成熟淋巴细胞和单核细胞，这可能会影响免疫重建和移植物抗宿主病（GVHD）。因此，我们在第一年对接受PBSCT的受者的免疫重建和细胞因子表达进行了连续评估。中性粒细胞和单核细胞的植入早期稳定，但自然杀伤（NK）细胞、B细胞和CD4+T细胞数量显著（P<0.05）偏低，CD4:CD8比值持续倒置。在第一年，NK功能一直较低。CD4+T细胞数量的定量减少导致对丝裂原和同种异体人白细胞抗原（alloHLA）抗原反应的增殖显著降低。然而，即使在移植后早期，通过抗CD3激活T细胞后Ca++内流测量的T细胞功能的定性分析以及丝裂原刺激的B细胞分泌的T细胞依赖性多克隆免疫球蛋白仍得以保留。在第一年，几乎所有受者都检测到肿瘤坏死因子α（TNFα）信使核糖核酸（mRNA）。在移植后的前6个月，77%的受者检测到白细胞介素10（IL-10）mRNA，22%检测到白细胞介素2（IL-2），44%检测到干扰素γ（IFNγ）mRNA。在移植后的第二个6个月，只有30%的受者表达IL-10，而分别有38%和46%的受者检测到IL-2和IFNγ的表达。37%的PBSCT受者发生了II-IV级急性GVHD，但72%的受者在中位120天时发展为慢性广泛性GVHD。62%的受者在PBSCT后的第一年发生了巨细胞病毒（CMV）病毒血症，5.4%发生了明显的CMV疾病。淋巴细胞植入在数量上延迟，但CD4功能得以保留，而PBSCT后NK数量和功能受损。移植后6个月后IL-10表达下降，而TNFα持续表达。淋巴细胞数量重建和淋巴细胞功能质量之间的平衡以及淋巴因子模式的变化可能会影响感染和GVHD，从而影响PBSCT后的临床结局。
