Mackall C L, Granger L, Sheard M A, Cepeda R, Gress R E
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD. 20892.
Blood. 1993 Oct 15;82(8):2585-94.
To study the source of regenerated T cells after bone marrow transplantation (BMT), lethally irradiated thymectomized and thymus-bearing C57BL/6 (Thy 1.2+) mice were injected with syngeneic T-cell depleted bone marrow (TCD BM) cells and graded numbers of congenic B6/Thy 1.1+ lymph node (LN) cells. LN cell expansion was the predominant source for T-cell regeneration in thymectomized hosts but was minimal in thymus-bearing hosts. Analysis of T-cell receptor (TCR) expression on LN progeny showed a diverse V beta repertoire. Therefore, peripheral T-cell progenitors exist within V beta families, but expansion of these progenitors after BMT is downregulated in the presence of a functional thymus. CD4+ cells derived from BM versus LN in thymus-bearing hosts displayed differential CD44 and CD45 isoform expression. BM-derived cells were primarily CD45RB+CD44lo and LN derived cells were nearly exclusively CD45RB- CD44hi. In thymectomized hosts, BM, host, and LN CD4+ progeny were CD45RB- CD44hi. We conclude that T-cell regeneration via peripheral T-cell progenitors predominates in hosts lacking thymic function and gives rise to T cells that display a "memory" phenotype. In contrast, the ability to generate sizable populations of "naive" type T cells after BMT appears limited to the prethymic progenitor pool and could serve as a marker for thymic regenerative capacity.
为研究骨髓移植（BMT）后再生T细胞的来源，对经致死剂量照射、切除胸腺以及保留胸腺的C57BL/6（Thy 1.2+）小鼠注射同基因T细胞清除的骨髓（TCD BM）细胞和不同数量的同基因B6/Thy 1.1+淋巴结（LN）细胞。在切除胸腺的宿主中，LN细胞扩增是T细胞再生的主要来源，但在保留胸腺的宿主中则极少。对LN子代细胞上T细胞受体（TCR）表达的分析显示出多样的Vβ谱系。因此，外周T细胞祖细胞存在于Vβ家族中，但在存在功能性胸腺的情况下，BMT后这些祖细胞的扩增受到下调。在保留胸腺的宿主中，源自BM与LN的CD4+细胞表现出不同的CD44和CD45异构体表达。源自BM的细胞主要是CD45RB+CD44lo，而源自LN的细胞几乎全是CD45RB- CD44hi。在切除胸腺的宿主中，BM、宿主和LN的CD4+子代细胞均为CD45RB- CD44hi。我们得出结论，在缺乏胸腺功能的宿主中，通过外周T细胞祖细胞进行的T细胞再生占主导，并产生表现出“记忆”表型的T细胞。相比之下，BMT后产生大量“幼稚”型T细胞的能力似乎仅限于胸腺前祖细胞池，并且可作为胸腺再生能力的一个标志。
