Galy A H, Cen D, Travis M, Chen S, Chen B P
Experimental Cellular Therapy Group, Systemix Inc, Palo Alto, CA 94304, USA.
Blood. 1995 May 15;85(10):2770-8.
T-cell production is largely dependent on the presence of a thymus gland where CD34+ precursors mature into T lymphocytes. Prethymic stages of T-cell development are less defined. Therefore, this study aims to delineate T-progenitor cell potential within the CD34+ Lineage--(Lin-) cell compartment of adult bone marrow (ABM). Fractionation of CD34+ Lin- ABM cells with CD45RA, Thy-1, CD38, and HLA-DR failed to absolutely segregate T-cell reconstituting ability, indicating broad distribution of T-progenitor cell potential. Titration experiments showed that low numbers of CD34+ Lin- CD45RA+ (RA+) cells had greater thymus repopulating ability than CD34+ Lin- CD45RA- cells (RA-). The great majority (> 95%) of RA+ cells expressed CD38, HLA-DR and 70% to 90% of RA+ cells lacked Thy-1 surface expression. RA+ cells contained colony-forming unit granulocyte-macrophage (CFU-GM) progenitor cells but were depleted of erythroid potential, did not provide hematopoietic reconstitution of human bone fragments implanted into SCID mice, and did not efficiently maintain CD34+ cells with secondary clonogenic potential in bone marrow cultures. Thus, RA+ cells are oligopotent (nonprimitive) CD34+ progenitors with T-cell reconstituting ability. In contrast, these same assays indicated that CD34+ Lin- CD45RA- cells (RA- cells) comprised hematopoietic stem cells (HSC) with primitive multilineage (T, B, myeloid, and erythroid) hematopoietic potential. It was confirmed that HSC-containing populations, such as CD34+ Lin- CD45RA- Thy-1+ cells had thymus repopulating ability. Culture of RA- cells on murine bone marrow stromal cells in the presence of interleukin (IL)-3, IL-6, and leukemia inhibitory factor (LIF) generated CD34+ CD45RA+ progeny engrafting in a secondary severe combined immunodeficiency (SCID)-hu thymus assay. Altogether, our results underscore the fact that T-cell reconstituting potential can be dissociated from HSC activity. Furthermore, we speculate that HSC might develop into the T lineage indirectly, via differentiation into an intermediate oligopotent CD34+ CD45RA+ stage. Finally, T-progenitor cells can be cultured in vitro.
T细胞的产生很大程度上依赖于胸腺的存在，在胸腺中CD34+前体细胞成熟为T淋巴细胞。T细胞发育的胸腺前阶段定义较少。因此，本研究旨在描绘成年骨髓（ABM）的CD34+谱系阴性（Lin-）细胞区室中的T祖细胞潜能。用CD45RA、Thy-1、CD38和HLA-DR对CD34+ Lin- ABM细胞进行分馏未能绝对分离T细胞重建能力，表明T祖细胞潜能分布广泛。滴定实验表明，少量的CD34+ Lin- CD45RA+（RA+）细胞比CD34+ Lin- CD45RA-细胞（RA-）具有更强的胸腺重建能力。绝大多数（>95%）的RA+细胞表达CD38、HLA-DR，70%至90%的RA+细胞缺乏Thy-1表面表达。RA+细胞含有集落形成单位粒细胞-巨噬细胞（CFU-GM）祖细胞，但缺乏红系潜能，不能为植入SCID小鼠的人骨碎片提供造血重建，也不能在骨髓培养中有效地维持具有二次克隆形成潜能的CD34+细胞。因此，RA+细胞是具有T细胞重建能力的寡能（非原始）CD34+祖细胞。相比之下，同样的检测表明，CD34+ Lin- CD45RA-细胞（RA-细胞）包含具有原始多谱系（T、B、髓系和红系）造血潜能的造血干细胞（HSC）。已证实含有HSC的群体，如CD34+ Lin- CD45RA- Thy-1+细胞具有胸腺重建能力。在白细胞介素（IL）-3、IL-6和白血病抑制因子（LIF）存在的情况下，将RA-细胞培养在小鼠骨髓基质细胞上，可产生能在二次严重联合免疫缺陷（SCID）-人胸腺检测中植入的CD34+ CD45RA+后代。总之，我们的结果强调了T细胞重建潜能可与HSC活性分离这一事实。此外，我们推测HSC可能通过分化为中间寡能的CD34+ CD45RA+阶段间接发育为T谱系。最后，T祖细胞可以在体外培养。
