Allogeneic reconstitution after nonmyeloablative conditioning: mitigation of graft‐versus‐host and host‐versus‐graft reactivity by anti‐CD44v6

T‐cell maturation is accelerated in transgenic mice expressingrat CD44v4‐v7 on T cells, the effect being blocked by anti‐CD44v6. Thisfinding suggested functional activity of CD44v6 in thymocytedevelopment. We tested the hypothesis by antibody blocking and usingmice with targeted deletion of CD44v6/v7 exon products(CD44v6/v7 −/− ). When lethally irradiatedCD44v6/v7‐competent (CD44v6/v7 +/+ ) mice were reconstitutedsyngeneically, higher numbers of CD44v6/v7 −/− thanCD44v6/v7 +/+ BMC were required for survival, the period ofreconstitution was prolonged, and regain of immunocompetence wasdelayed. Similar findings were observed in lethally irradiated, anti‐CD44v6‐treated syngeneic CD44v6/v7 +/+ hosts. Thus, CD44v6/v7 supports maturation and expansion of hematopoietic progenitorcells. Surprisingly, reconstitution with CD44v6/v7 −/− BMCor anti‐CD44v6 treatment of the nonlethally irradiated allogeneicCD44v6/v7 +/+ host had only a minor impact on survivalrates. When nonlethally irradiated CD44v6/v7 −/− hostsreceived an allogeneic graft, survival rates were improved. Thesephenomena have been a result of reduced GvH reactivities when the donorwas CD44v6/v7 −/− and reduced HvG reactivities in the CD44v6/v7 −/− host. Thus, although a deficit or blockadeof CD44v6/v7 has a negative impact on hematopoietic reconstitution, atransient blockade will be of benefit for the allogeneicallyreconstituted host because of a strong reduction in GvH and HvGreactivities.