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The Journal of Immunology, Vol 150, Issue 2 447-455, Copyright © 1993 by American Association of Immunologists
ARTICLES |
T Suda and A Zlotnik
DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304.
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.
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