Suda T, Zlotnik A
DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304.
J Immunol. 1993 Jan 15;150(2):447-55.
It has been widely accepted that CD3+CD4-CD8- T cells expressing TCR-alpha beta or TCR-gamma delta (found in the thymus as well as in the periphery) represent lineages distinct from either CD4+CD8- and CD4-CD8+ single-positive T cells expressing TCR-alpha beta. However, the origin, differentiation pathway, and TCR-repertoire selection of CD3+CD4-CD8- T cells remain controversial. We demonstrate that CD3+CD4-CD8- thymocytes can be separated into three subsets based on their expression of heat-stable Ag (HSA) and CD44. Our results further suggest the following: 1) the HSA+ subset represents a pre-selection population, although the HSA- subset is a postselection subset; 2) the high incidence of V beta 8.2 usage among CD3+CD4-CD8- thymocytes is a result of positive selection, rather than a predetermined event at a precursor cell level; 3) the maturation of CD3+CD4-CD8- thymocytes proceeds along the following differentiation pathway: HSA+CD44(-)-->HSA-CD44(-)-->HSA-CD44+. Both TCR-alpha beta +CD4-CD8- and TCR-gamma delta +CD4-CD8- thymocytes show similar differentiation processes; 4) CD3+CD4-CD8-cells directly differentiate from CD25+CD3-CD4-CD8- thymocytes which include precursor cells for both the CD3+CD4-CD8- and the CD4+CD8-/CD4-CD8+ lineages. Taken together, these results suggest that the CD25+CD3-CD4-CD8- stage of thymocyte differentiation represents a branching point for either the CD4+CD8- or CD4-CD8+ single-positive lineages or the CD3+CD4-CD8- lineages.
表达TCR-αβ或TCR-γδ的CD3⁺CD4⁻CD8⁻T细胞（在胸腺和外周均有发现）代表了与表达TCR-αβ的CD4⁺CD8⁻和CD4⁻CD8⁺单阳性T细胞不同的谱系，这一观点已被广泛接受。然而，CD3⁺CD4⁻CD8⁻T细胞的起源、分化途径和TCR库选择仍存在争议。我们证明，CD3⁺CD4⁻CD8⁻胸腺细胞可根据其热稳定抗原（HSA）和CD44的表达分为三个亚群。我们的结果进一步表明：1）HSA⁺亚群代表预选群体，而HSA⁻亚群是选后亚群；2）CD3⁺CD4⁻CD8⁻胸腺细胞中Vβ8.2使用频率高是阳性选择的结果，而非前体细胞水平的预先决定事件；3）CD3⁺CD4⁻CD8⁻胸腺细胞的成熟沿着以下分化途径进行：HSA⁺CD44⁻→HSA⁻CD44⁻→HSA⁻CD44⁺。TCR-αβ⁺CD4⁻CD8⁻和TCR-γδ⁺CD4⁻CD8⁻胸腺细胞均显示相似的分化过程；4）CD3⁺CD4⁻CD8⁻细胞直接从CD25⁺CD3⁻CD4⁻CD8⁻胸腺细胞分化而来，后者包括CD3⁺CD4⁻CD8⁻以及CD4⁺CD8⁻/CD4⁻CD8⁺谱系的前体细胞。综上所述，这些结果表明胸腺细胞分化的CD25⁺CD3⁻CD4⁻CD8⁻阶段代表了CD4⁺CD8⁻或CD4⁻CD8⁺单阳性谱系或CD3⁺CD4⁻CD8⁻谱系的分支点。
