TREATMENT OF MICE WITH ANTI-CD44 AFTER ALLOGENEIC BONE-MARROW CELL TRANSPLANTATION IS LETHAL

Because CD44 is known to be of functional importance in hematopoiesis, we were interested in whether anti-CD44 would interfere with syngenei c or allogeneic bone marrow cell engraftment. Syngeneic and allogeneic grafts were accepted by over 80% of mice. In both the syngeneic and t he allogeneic host, homing, repopulation, and regain of immunoreactivi ty was delayed by anti-CD44 treatment. But in the syngeneic host the o verall survival rate was unaltered. Instead, less than 25% of anti-CD4 4-treated, allogeneically reconstituted mice survived by recovery of t he host's hematopoietic system, i.e. graft acceptance was close to 0%. The mice died between 4 and 15 days after engraftment and showed seve re alterations of the gut. The high death rate of the allogeneically r econstituted mice was specific for anti-CD44 treatment. It did not dep end on an ADCC mechanism, could not be abrogated by depletion of T cel ls, and was only mitigated by depletion of NK cells. According to the histological appearance of the gut, anti-CD44 strengthens a local (gut -associated) graft versus host reaction, which is not mediated by alph a beta T cells and at least not exclusively by NK cells. Because gut d eath is one of the major reasons for failure in allogeneic bone marrow transplantation, the model of anti-CD44-induced lethality offers itse lf to clarify the underlying mechanism.