Dumont-Girard F, Roux E, van Lier R A, Hale G, Helg C, Chapuis B, Starobinski M, Roosnek E
Division of Immunology, the Division of Oncology and the Division of Hematology, the Department of Internal Medicine, Hôpital Cantonal Universitaire, Geneva, Switzerland.
Blood. 1998 Dec 1;92(11):4464-71.
We have studied the reconstitution of the T-cell compartment after bone marrow transplantation (BMT) in five patients who received a graft-versus-host disease (GVHD) prophylaxis consisting of methotrexate, cyclosporin, and 10 daily injections (day -4 to day +5) of Campath-1G. This treatment eliminated virtually all T cells (7 +/- 8 T cells/microL at day 14) which facilitated the analysis of the thymus-dependent and independent pathways of T-cell regeneration. During the first 6 months, the peripheral T-cell pool was repopulated exclusively through expansion of residual T cells with all CD4(+) T cells expressing the CD45RO-memory marker. In two patients, the expansion was extensive and within 2 months, the total number of T cells (CD8>>CD4) exceeded 1,000/microL. In the other three patients, T cells remained low (87 +/- 64 T cells/microL at 6 months) and remained below normal values during the 2 years of the study. In all patients, the first CD4(+)CD45RA+RO- T cells appeared after 6 months and accumulated thereafter. In the youngest patient (age 13), the increase was relatively fast and naive CD4(+) T cells reached normal levels (600 T cells/microL) 1 year later. In the four adult patients (age 25 +/- 5), the levels reached at that time-point were significantly lower (71 +/- 50 T cells/microL). In all patients, the T-cell repertoire that had been very limited, diversified with the advent of the CD4(+)CD45RA+RO- T cells. Cell sorting experiments showed that this could be attributed to the complexity of the T-cell repertoire of the CD4(+)CD45RA+RO- T cells that was comparable to that of a normal individual and that, therefore, it is likely that these cells are thymic emigrants. We conclude that after BMT, the thymus is essential for the restoration of the T-cell repertoire. Because the thymic activity is restored with a lag time of approximately 6 months, this might explain why, in particular in recipients of a T-cell-depleted graft, immune recovery is delayed.
我们研究了5例接受骨髓移植（BMT）患者的T细胞区室重建情况，这些患者接受了由甲氨蝶呤、环孢素以及在第-4天至第+5天每日注射1次（共10次）Campath-1G组成的移植物抗宿主病（GVHD）预防方案。这种治疗几乎清除了所有T细胞（第14天时为7±8个T细胞/微升），这便于分析T细胞再生的胸腺依赖和非胸腺依赖途径。在最初的6个月里，外周T细胞库完全通过残留T细胞的扩增得以重建，所有CD4(+) T细胞均表达CD45RO记忆标记。在2例患者中，扩增广泛，2个月内T细胞总数（CD8>>CD4）超过1000个/微升。在另外3例患者中，T细胞数量仍然较低（6个月时为87±64个T细胞/微升），且在研究的2年期间一直低于正常值。在所有患者中，首批CD4(+)CD45RA+RO- T细胞在6个月后出现并随后积累。在最年轻的患者（13岁）中，增长相对较快，1年后幼稚CD4(+) T细胞达到正常水平（600个T细胞/微升）。在4例成年患者（25±5岁）中，该时间点达到的水平明显较低（71±50个T细胞/微升）。在所有患者中，原本非常有限的T细胞库随着CD4(+)CD45RA+RO- T细胞的出现而多样化。细胞分选实验表明，这可能归因于CD4(+)CD45RA+RO- T细胞T细胞库的复杂性，其与正常个体相当，因此，这些细胞很可能是胸腺迁出细胞。我们得出结论，骨髓移植后，胸腺对于T细胞库的恢复至关重要。由于胸腺活性的恢复有大约6个月的延迟时间，这可能解释了为什么，特别是在接受T细胞清除移植物的受者中，免疫恢复会延迟。
