Treatment of mice with anti-CD44 after allogeneic bone marrow cell transplantation is lethal.

Abstract

Because CD44 is known to be of functional importance in hematopoiesis, we were interested in whether anti-CD44 would interfere with syngeneic or allogeneic bone marrow cell engraftment. Syngeneic and allogeneic grafts were accepted by over 80% of mice. In both the syngeneic and the allogeneic host, homing, repopulation, and regain of immunoreactivity was delayed by anti-CD44 treatment. But in the syngeneic host the overall survival rate was unaltered. Instead, less than 25% of anti-CD44-treated, allogeneically reconstituted mice survived by recovery of the host's hematopoietic system, i.e. graft acceptance was close to 0%. The mice died between 4 and 15 days after engraftment and showed severe alterations of the gut. The high death rate of the allogeneically reconstituted mice was specific for anti-CD44 treatment. It did not depend on an ADCC mechanism, could not be abrogated by depletion of T cells, 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 alphabeta T cells and at least not exclusively by NK cells. Because gut death is one of the major reasons for failure in allogeneic bone marrow transplantation, the model of anti-CD44-induced lethality offers itself to clarify the underlying mechanism.