Improved survival from potentially lethal graft‐vs.‐host disease by donor pretreatment with a recipient‐specific blood transfusion. II. Evidence for a principal role of the CD4⁺ T cell subset

Abstract

Pretreatment of prospective donors of hemopoietic cells with a single recipient-specific blood transfusion can significantly decrease the morbidity and mortality of potentially lethal graft-vs.-host disease (GVHD) in lethally irradiated, allogeneically reconstituted mice. In a previous report we described the requirements for induction of this blood transfusion effect. In the present study we addressed in particular the mechanism underlying this effect. The beneficial effect of blood transfusion appeared to be due to the white blood cell population in the transfused blood. X-irradiation (20 Gy) of the blood prior to transfusion did not abrogate the effect, which makes a veto cell mechanism unlikely. The blood transfusion effect in this model appeared to be mediated by the CD4+ T cell subset, since purified CD4+ spleen cells from transfused donors caused considerably less morbidity and mortality than naive CD4+ spleen cells. Apparently CD8+ cells were not involved, because their absence did not affect the beneficial effect. This observation was further confirmed by the finding that treatment of recipient mice that were reconstituted with spleen cells from transfused donors with anti-CD8 monoclonal antibody (mAb) did not abrogate the blood transfusion effect. Interestingly, the blood transfusion effect was enhanced by administration of anti-CD4 mAb to the recipients. The anti-CD4 mAb might impair the interaction between T cells and antigen-presenting cells, resulting in functional inactivation.