Immature human thymocytes can be driven to differentiate into nonlymphoid lineages by cytokines from thymic epithelial cells.
Immature human thymocytes can be driven to differentiate into nonlymphoid lineages by cytokines from thymic epithelial cells.
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未成熟的人类胸腺细胞可以被胸腺上皮细胞的细胞因子驱动分化为非淋巴谱系。
DOI：
10.1073/pnas.86.19.7575
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发表时间：
1989
影响因子：
11.1
通讯作者：
Haynes,BF
中科院分区：
文献类型：
--
作者：
Kurtzberg,J;Denning,SM;Nycum,LM;Singer,KH;Haynes,BF
造血干细胞向T细胞系定型所需的信号和细胞相互作用尚不清楚，但对于理解正常T细胞发育的早期阶段至关重要。为了研究T细胞前体的分化能力，我们从出生后的人胸腺中分离出CD 4-、CD 8-、表面CD 3-胸腺细胞，并测定它们在体外分化为淋巴和非淋巴谱系的能力。我们发现，CD 4-，CD 8-，sCD 3-胸腺细胞，在T细胞条件培养基加白细胞介素2的存在下分化成表达γ δ受体抗原的T细胞，能够分化成髓系或红系细胞系在5637膀胱癌细胞系条件培养基加重组人促红细胞生成素或人胸腺上皮细胞条件培养基的存在下。胸腺上皮细胞条件培养液与5637上清加促红细胞生成素诱导CD_4 ~-、CD_8 ~-、CD_3 ~-胸腺细胞向髓系红细胞分化的效果相当。用5637上清液加促红细胞生成素培养4天，68 +/- 14%的CD 4-、CD 8-、sCD 3-胸腺细胞经历非淋巴样分化。新鲜分离的CD 4-、CD 8-、sCD 3-胸腺细胞中CD 34+细胞占26 +/-4%，克隆性粒/巨噬细胞、粒/红细胞/单核细胞/巨核细胞和T祖细胞在CD 4-、CD 8-、sCD 3-胸腺细胞的CD 34+和CD 34-亚群中均存在。因此，人CD 4-、CD 8-、sCD 3-胸腺细胞亚群内的细胞可产生γ δ + T细胞以及骨髓红细胞谱系的细胞。此外，CD 34+、CD 4-、CD 8-、sCD 3-细胞可以产生克隆的T细胞祖细胞以及克隆的髓样祖细胞。
The signals and cellular interactions required for hematopoietic stem-cell commitment to the T lineage are unknown, yet are central to understanding the early stages of normal T-cell development. To study the differentiative capacity of T-cell precursors, we isolated CD4-, CD8-, surface(s) CD3- thymocytes from postnatal human thymuses and determined their capacity to differentiate into lymphoid and nonlymphoid lineages in vitro. We found that CD4-, CD8-, sCD3- thymocytes, which differentiated in the presence of T-cell conditioned medium plus interleukin 2 into T cells expressing the gamma delta receptor for antigen, were capable of differentiating into myeloid or erythroid lineages in the presence of either 5637 bladder carcinoma cell line conditioned medium plus recombinant human erythropoietin or human thymic epithelial cell conditioned medium. Thymic epithelial cell conditioned medium was as effective as 5637 supernatant plus erythropoietin in inducing myeloerythroid differentiation in the CD4-, CD8-, sCD3- thymocytes. Sixty-eight +/- 14% of CD4-, CD8-, sCD3- thymocytes underwent nonlymphoid differentiation within 4 days in culture with 5637 supernatant plus erythropoietin. Twenty-six +/- 4% of freshly isolated CD4-, CD8-, sCD3- cells were CD34+, and clonal granulocyte/macrophage, granulocyte/erythrocyte/monocyte/megakaryocyte, and T-cell progenitors were found in both CD34+ and CD34- subsets of CD4-, CD8-, sCD3- thymocytes. Thus, cells within the human CD4-, CD8-, sCD3- thymocyte subset can give rise to gamma delta+ T cells as well as to cells of myeloerythroid lineages. Moreover, CD34+, CD4-, CD8-, sCD3- cells can give rise to clonal T-cell progenitors as well as to clonal myeloid progenitors.