未处理、CD8 细胞耗竭或 CD34 选择的非清髓性外周血干细胞移植后的 T 细胞重建。

T-cell reconstitution after unmanipulated, CD8-depleted or CD34-selected nonmyeloablative peripheral blood stem-cell transplantation.

作者信息

Baron Frédéric, Schaaf-Lafontaine Nicole, Humblet-Baron Stéphanie, Meuris Nathalie, Castermans Emilie, Baudoux Etienne, Frère Pascale, Bours Vincent, Fillet Georges, Beguin Yves

机构信息

Department of Medicine, Division of Hematology, University of Liège, CHU Sart-Tilman, 4000 Liège, Belgium.

出版信息

Transplantation. 2003 Dec 27;76(12):1705-13. doi: 10.1097/01.TP.0000093987.11389.F7.

DOI:10.1097/01.TP.0000093987.11389.F7

PMID:14688520

Abstract

BACKGROUND

We have previously shown that CD8 depletion or CD34 selection of peripheral blood stem cells (PBSC) reduced the incidence of acute graft-versus-host disease (GvHD) after nonmyeloablative stem-cell transplantation (NMSCT). In this study, we analyze the effect of CD8 depletion or CD34 selection of the graft on early T-cell reconstitution.

METHODS

Nonmyeloablative conditioning regimen consisted in 2 Gy total-body irradiation (TBI) alone, 2 Gy TBI and fludarabine, or cyclophosphamide and fludarabine. Patients 1 to 18 received unmanipulated PBSC, patients 19 to 29 CD8-depleted PBSC, and patients 30 to 35 CD34-selected PBSC.

RESULTS

T-cell counts, and particularly CD4+ and CD4CD45RA+ counts, remained low the first 6 months after nonmyeloablative stem-cell transplantation (NMSCT) in all patients. CD34 selection (P<0.0001) but not CD8 depletion of PBSC significantly decreased T-cell chimerism. Donor T-cell count was similar in unmanipulated compared with CD8-depleted PBSC recipients but was significantly lower in CD34-selected PBSC recipients (P=0.0012). T cells of recipient origin remained stable over time in unmanipulated and CD8-depleted PBSC patients but expanded in some CD34-selected PBSC recipients between day 28 and 100 after transplant. Moreover, whereas CD8 depletion only decreased CD8+ counts (P<0.047), CD34 selection reduced CD3+(P<0.001), CD8+(P<0.016), CD4+ (P<0.001), and CD4+CD45RA+ (P<0.001) cell counts. T-cell repertoire was restricted in all patients on day 100 after hematopoietic stem-cell transplantation but was even more limited after CD34 selection (P=0.002).

CONCLUSIONS

Despite of the persistence of a significant number of T cells of recipient origin, T-cell counts were low the first 6 months after NMSCT. Moreover, contrary with CD8 depletion of the graft that only affects CD8+ lymphocyte counts, CD34 selection dramatically decreased both CD8 and CD4 counts.

摘要

背景

我们之前已经表明，对外周血干细胞（PBSC）进行CD8细胞清除或CD34分选可降低非清髓性干细胞移植（NMSCT）后急性移植物抗宿主病（GvHD）的发生率。在本研究中，我们分析了移植物的CD8细胞清除或CD34分选对早期T细胞重建的影响。

方法

非清髓性预处理方案包括单独2 Gy全身照射（TBI）、2 Gy TBI联合氟达拉滨，或环磷酰胺联合氟达拉滨。患者1至18接受未处理的PBSC，患者19至29接受CD8细胞清除的PBSC，患者30至35接受CD34分选的PBSC。

结果

在所有患者中，非清髓性干细胞移植（NMSCT）后的前6个月，T细胞计数，尤其是CD4+和CD4CD45RA+计数仍维持在较低水平。PBSC的CD34分选（P<0.0001）而非CD8细胞清除显著降低了T细胞嵌合率。与接受CD8细胞清除的PBSC的受者相比，接受未处理的PBSC的受者的供体T细胞计数相似，但接受CD34分选的PBSC的受者的供体T细胞计数显著更低（P=0.0012）。在接受未处理的PBSC和CD8细胞清除的PBSC的患者中，受者来源的T细胞随时间保持稳定，但在移植后第28天至100天之间，一些接受CD34分选的PBSC的受者中其T细胞有所扩增。此外，虽然CD8细胞清除仅降低了CD8+计数（P<0.047），但CD34分选降低了CD3+（P<0.001）、CD8+（P<0.016）、CD4+（P<0.001）和CD4+CD45RA+（P<0.001）细胞计数。造血干细胞移植后第100天，所有患者的T细胞库均受限，但在CD34分选后更为受限（P=0.002）。