人类CD69⁺CD3⁺胸腺细胞分化过程中不同阶段的特征描述及胸腺迁出细胞的鉴定。

Characterization of distinct stages during the differentiation of human CD69+CD3+ thymocytes and identification of thymic emigrants.

作者信息

Vanhecke D, Leclercq G, Plum J, Vandekerckhove B

机构信息

Department of Clinical Biology, Microbiology and Immunology, University Hospital, Ghent, Belgium.

出版信息

J Immunol. 1995 Aug 15;155(4):1862-72.

PMID:7543535

Abstract

During thymocyte development, CD69 expression is induced at an early stage of positive selection. To examine the differentiation of human CD69+CD3+ thymocytes, discrete phenotypes were defined by the relative expression of CD69, CD27, CD1, and CD45RA/RO: CD3+CD69- thymocytes were CD27-CD1+CD45RA-/RO+ (phenotype I), whereas the CD3+ CD69+ population could be subdivided into CD27-CD1+CD45RA-/RA+ (phenotype II), CD27+CD1+CD45RA-/RO+ (phenotype III), CD27+CD1-CD45RA-/dull/RO+ (phenotype IV), and CD27+CD1-CD45RA+/ROdull (phenotype V) thymocytes. Phenotype I thymocytes were CD4+CD8 alpha beta + double positive (DP). Phenotype II thymocytes contained DP and CD4+CD8 alpha dullCD8 beta- cells, whereas phenotype III thymocytes were DP and mostly CD4dullCD8 alpha beta+, indicating that CD27 on DP cells may be a marker for CD8-committed cells. Results obtained with SCID-hu mice, transplanted with human fetal thymus and liver, showed that immature human CD69-CD3+ thymocytes were corticosteroid-sensitive, whereas essentially all CD69+CD3+ cells were resistant. During differentiation of one cohort of corticosteroid-resistant CD69+CD3+ thymocytes, phenotype II and III thymocytes, disappeared within a week, whereas the percentage of phenotype IV and especially V thymocytes increased, suggesting that the latter represent the end stages in differentiation. Recent thymic emigrants in SCID-hu mice were identified as CD69-CD27+CD1-CD45RA-/dull/RO+ or CD45RA+/ROdull cells. Because phenotype IV and phenotype V thymocytes rapidly lose CD69 expression in cell culture, these thymocytes are probably the cells that are exported from the thymus. In conclusion, after the acquisition of CD69, thymocyte differentiation appears to continue in an ordered pattern, and cells that eventually leave the thymus are CD69-CD1-CD45RA+ or CD45RA-/dull.

摘要

在胸腺细胞发育过程中，CD69表达在阳性选择的早期阶段被诱导。为了研究人CD69⁺CD3⁺胸腺细胞的分化，通过CD69、CD27、CD1和CD45RA/RO的相对表达来定义不同的表型：CD3⁺CD69⁻胸腺细胞为CD27⁻CD1⁺CD45RA⁻/RO⁺（表型I），而CD3⁺CD69⁺群体可细分为CD27⁻CD1⁺CD45RA⁻/RA⁺（表型II）、CD27⁺CD1⁺CD45RA⁻/RO⁺（表型III）、CD27⁺CD1⁻CD45RA⁻/ dull/RO⁺（表型IV）和CD27⁺CD1⁻CD45RA⁺/ROdull（表型V）胸腺细胞。表型I胸腺细胞为CD4⁺CD8αβ⁺双阳性（DP）。表型II胸腺细胞包含DP和CD4⁺CD8αdullCD8β⁻细胞，而表型III胸腺细胞为DP且大多为CD4dullCD8αβ⁺，表明DP细胞上的CD27可能是CD8定向细胞的标志物。用人胎儿胸腺和肝脏移植的SCID-hu小鼠实验结果表明，未成熟的人CD69⁻CD3⁺胸腺细胞对皮质类固醇敏感，而基本上所有CD69⁺CD3⁺细胞都具有抗性。在一组对皮质类固醇有抗性的CD69⁺CD3⁺胸腺细胞分化过程中，表型II和III胸腺细胞在一周内消失，而表型IV尤其是V胸腺细胞的百分比增加，这表明后者代表分化的终末阶段。SCID-hu小鼠中的近期胸腺迁出细胞被鉴定为CD69⁻CD27⁺CD1⁻CD45RA⁻/dull/RO⁺或CD45RA⁺/ROdull细胞。由于表型IV和表型V胸腺细胞在细胞培养中会迅速失去CD69表达，这些胸腺细胞可能是从胸腺输出的细胞。总之，在获得CD69后，胸腺细胞分化似乎以有序模式继续，最终离开胸腺的细胞是CD69⁻CD1⁻CD45RA⁺或CD45RA⁻/dull。