Roux E, Dumont-Girard F, Starobinski M, Siegrist C A, Helg C, Chapuis B, Roosnek E
Division of Immunology and Allergology, Department of Internal Medicine, University Hospital, Geneva, Switzerland.
Blood. 2000 Sep 15;96(6):2299-303.
To evaluate the importance of the thymus for the reconstitution of immunity in recipients of a T-cell-depleted bone marrow, we measured the appearance of CD4(+)CD45RA(+)RO(-) naive T cells (thymic rebound), restoration of the diversity of the T-cell-receptor (TCR) repertoire and the response to vaccinations with tetanus toxoid (TT). Repopulation by CD4(+)CD45RA(+)RO(-) thymic emigrants varied among patients, starting at approximately 6 months after transplantation. Young patients reconstituted swiftly, whereas in older patients, the recovery of normal numbers of naive CD4(+) T cells could take several years. Restoration of TCR diversity was correlated with the number of naive CD4(+)CD45RA(+)RO(-) T cells. Moreover, the extent of the thymic rebound correlated with the patient's capacity to respond to vaccinations. Patients without a significant thymic rebound at the moment of vaccination (CD4(+)CD45RA(+)RO(-) T cells less than 30 microL) did not respond, or responded only marginally even after 3 boosts with TT. We conclude that during the first year after transplantation, the absence of an immune response is due mainly to the loss of an adequate T-cell repertoire. Restoration of the repertoire can come only from a thymic rebound that can be monitored by measuring the increase of CD4(+)CD45RA(+)RO(-) naive T cells. This will allow postponing revaccinations to a moment when the patient will be able to respond more effectively. This may be particularly useful in the elderly patient who, owing to low thymic activity, might not yet be able to respond 1 year after transplant when revaccinations are usually scheduled.
为评估胸腺对T细胞清除的骨髓移植受者免疫重建的重要性，我们检测了CD4(+)CD45RA(+)RO(-)幼稚T细胞的出现（胸腺反弹）、T细胞受体（TCR）库多样性的恢复以及对破伤风类毒素（TT）疫苗接种的反应。CD4(+)CD45RA(+)RO(-)胸腺迁出细胞的再填充在患者中各不相同，始于移植后约6个月。年轻患者迅速重建，而老年患者中，幼稚CD4(+) T细胞恢复到正常数量可能需要数年时间。TCR多样性的恢复与幼稚CD4(+)CD45RA(+)RO(-) T细胞的数量相关。此外，胸腺反弹的程度与患者对疫苗接种的反应能力相关。在接种疫苗时没有明显胸腺反弹的患者（CD4(+)CD45RA(+)RO(-) T细胞少于30 μL）没有反应，或者即使在3次TT加强接种后也仅产生微弱反应。我们得出结论，在移植后的第一年，免疫反应缺失主要是由于缺乏足够的T细胞库。库的恢复只能来自胸腺反弹，可通过检测CD4(+)CD45RA(+)RO(-)幼稚T细胞的增加来监测。这将允许将再次接种推迟到患者能够更有效反应的时刻。这在老年患者中可能特别有用，由于胸腺活性低，他们在移植后1年通常安排再次接种时可能还无法产生反应。
