Characterization of distinct stages during the differentiation of human CD69+CD3+ thymocytes and identification of thymic emigrants
Vanhecke, D.; Leclercq, G.; Plum, J.; Vandekerckhove, B.
Journal of Immunology 155(4): 1862-1872
1995
ISSN/ISBN: 0022-1767 PMID: 7543535 Document Number: 443524
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-/RO+ (phenotype II), CD27+CD1+CD45RA-/RO- (phenotype II), CD27+CD1-CD45RA-/dull/RO+ (phenotype IV), and CD27+CD1-CD45RA+/RO-dull (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, wehreas phenotype III thymocytes were DP and mostly CD4-dullCD8-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, phenotypes 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+/+RO-dulL 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.