Variant isoforms of CD44 are required in early thymocyte development

The earliest T cells homing to the thymus (CD3(-)CD4(lo)CD8(-)) express CD1 17 (c-kit), CD43 (leukosialin), and the integrins CD11a (alpha (L)) CD11b ( alpha (M)), CD29 (beta (1)), CD49f (alpha (6)), and CD44. Using reagents sp ecific for CD44 variant isoforms (CD44v), we demonstrated that CID44v were expressed on virtually all early thymocytes, whereas cells carrying only th e standard molecule (CD44s, not containing any variant domains), which is u biquitously found on mature lymphocytes later, are very sparse. The express ion of CD44v was closely correlated with CD43 and CD117 and was restricted to the CD3(-)CD4(lo)CD8(-) stage. CD44v were detected on lymphocyte progeni tor populations in the fetal blood, liver, thymus and spleen, as well as in the adult bone marrow. Functional studies demonstrated that only cells exp ressing CD44v from fetal liver and adult bone marrow could efficiently popu late fetal thymic stroma and develop into mature T cells. In fetal thymic o rgan cultures anti-CD44v antibodies specifically blocked thymocyte developm ent. We also present evidence that CID44v were required for the initial int eraction of hematopoietic progenitor cells with the thymic stroma. Our data imply that CD44v are not only a useful marker for hematopoietic progenitor s, but also play a functional role in the initiation of thymocyte developme nt.