Variant isoforms of CD44 are required in early thymocyte development

The earliest T cells homing to the thymus (CD3-CD4loCD8-) express CD117 (c-kit), CD43 (leukosialin), and the integrins CD11a (alphaL), CD11b (alphaM), CD29 (beta1), CD49f (alpha6), and CD44. Using reagents specific for CD44 variant isoforms (CD44v), we demonstrated that CD44v were expressed on virtually all early thymocytes,whereas cells carrying only the standard molecule (CD44s, not containing any variant domains), which is ubiquitously found on mature lymphocytes later, are very sparse. The expression of CD44v was closely correlated with CD43 and CD117 and was restricted to the CD3-CD4loCD8- stage. CD44v were detected on lymphocyte progenitor populations in the fetal blood, liver, thymus and spleen, as well as in the adult bone marrow. Functional studies demonstrated that only cells expressing CD44v from fetal liver and adult bone marrow could efficiently populate fetal thymic stroma and develop into mature T cells. In fetal thymic organ cultures anti-CD44v antibodies specifically blocked thymocyte development. We also present evidence that CD44v were required for the initial interaction of hematopoietic progenitor cells with the thymic stroma. Our data imply that CD44v are not only a useful marker for hematopoietic progenitors, but also play a functional role in the initiation of thymocyte development.