Junge Sonja, Kloeckener-Gruissem Barbara, Zufferey Romain, Keisker Andre, Salgo Bettina, Fauchere Jean-Claude, Scherer Franziska, Shalaby Tarek, Grotzer Michael, Siler Ulrich, Seger Reinhard, Güngör Tayfun
Division of Immunology/Hematology/BMT, University Children's Hospital, Zürich, Switzerland.
Eur J Immunol. 2007 Nov;37(11):3270-80. doi: 10.1002/eji.200636976.
CD31(+)CD45RA(+)RO(-) lymphocytes contain high numbers of T cell receptor circle (TREC)-bearing T cells; however, the correlation between CD31(+)CD4(+) lymphocytes and TREC during aging and under lymphopenic conditions has not yet been sufficiently investigated. We analyzed TREC, telomere length and telomerase activity within sorted CD31(+) and CD31(-) CD4(+) lymphocytes in healthy individuals from birth to old age. Sorted CD31(+)CD45RA(+)RO(-) naive CD4(+) lymphocytes contained high TREC numbers, whereas CD31(+)CD45RA(-)RO(+) cells (comprising < or =5% of CD4(+) cells during aging) did not contain TREC. CD31(+) overall CD4(+) cells remained TREC rich despite an age-related tenfold reduction from neonatal (100 : 1000) to old age (10 : 1000). Besides a high TREC content, CD31(+)CD45RA(+)RO(-)CD4(+) cells exhibited significantly longer telomeres and higher telomerase activity than CD31(-)CD45RA(+)RO(-)CD4(+) cells, suggesting that CD31(+)CD45RA(+)RO(-)CD4(+) cells represent a distinct population of naive T cells with particularly low replicative history. To analyze the value of CD31 in lymphopenic conditions, we investigated six children after allogeneic hematopoietic stem cell transplantation (HSCT). Reemerging overall CD4(+) as well as naive CD45RA(+)RO(-)CD4(+) cells predominantly expressed CD31 and correlated well with the recurrence of TREC 5-12 months after HSCT. Irrespective of limitations in the elderly, CD31 is an appropriate marker to monitor TREC-rich lymphocytes essentially in lymphopenic children after HSCT.
CD31(+)CD45RA(+)RO(-)淋巴细胞含有大量携带T细胞受体环(TREC)的T细胞;然而,在衰老和淋巴细胞减少的情况下,CD31(+)CD4(+)淋巴细胞与TREC之间的相关性尚未得到充分研究。我们分析了从出生到老年的健康个体中,分选的CD31(+)和CD31(-) CD4(+)淋巴细胞内的TREC、端粒长度和端粒酶活性。分选的CD31(+)CD45RA(+)RO(-)初始CD4(+)淋巴细胞含有高数量的TREC,而CD31(+)CD45RA(-)RO(+)细胞(在衰老过程中占CD4(+)细胞的≤5%)不含TREC。尽管从新生儿期(100:1000)到老年期(10:1000),CD31(+)总体CD4(+)细胞中的TREC含量随年龄增长减少了10倍,但仍富含TREC。除了TREC含量高外,CD31(+)CD45RA(+)RO(-)CD4(+)细胞的端粒明显长于CD31(-)CD45RA(+)RO(-)CD4(+)细胞,端粒酶活性也更高,这表明CD31(+)CD45RA(+)RO(-)CD4(+)细胞代表了具有特别低复制史的独特初始T细胞群体。为了分析CD31在淋巴细胞减少情况下的价值,我们研究了6名接受异基因造血干细胞移植(HSCT)后的儿童。重新出现的总体CD4(+)以及初始CD45RA(+)RO(-)CD4(+)细胞主要表达CD31,并且与HSCT后5 - 12个月TREC的重现密切相关。尽管在老年人中有局限性,但CD31是监测HSCT后淋巴细胞减少的儿童中富含TREC的淋巴细胞的合适标志物。