Regain of immunocompetence after myeloablation and bone marrow cell (BMC) 
reconstitution essentially depends on T progenitor homing into the thymus and 
intrathymic T cell maturation. CD44 facilitates progenitor homing and settlement 
in the bone marrow and is known as a T progenitor marker. In search for 
improving regain of immunocompetence after BMC reconstitution, we explored 
whether the CD44 standard (CD44 s) and/or variant isoforms CD44v6 and CD44v7 
contribute to thymus repopulation and thymocyte maturation. Antibody-blocking 
studies and cells/mice with a targeted deletion of CD44v6/7 or CD44v7 revealed 
that CD44s, but not CD44v6 and CD44v7, has a major impact on progenitor cell 
homing into the thymus. Instead, CD44v6 strengthens apoptosis resistance and 
expansion of early thymocytes. CD44v6-induced apoptosis resistance, most strong 
in double-negative (DN) thymocytes, is accompanied by Akt activation. 
CD44v6-induced proliferation of DN cells proceeds via activation of the MAPK 
pathway. At later stages of T cell maturation, CD44 acts as an accessory 
molecule, initiating and supporting TCR/CD3 complex-mediated signal transduction 
in double-positive and single-positive thymocytes. Thus, CD44 plays a major role 
in thymus homing. In addition, CD44v6 is important for survival and expansion of 
early thymocytes. These findings suggest that strengthening CD44v6 expression on 
lymphoid progenitors could well contribute to accelerated regain of 
immunocompetence.