SI05 Peptide Therapy Suppresses the Adverse Immune Response to Red Cells

Abstract

RhD is a clinically important blood group and a major target in haemolytic disease of the newborn (HDN). Current anti‐D antibody therapy to prevent antibody production in RhD negative mothers is ineffective if there has already been sensitization. Peptide immunotherapy offers an alternative approach. Helper T cell epitopes of the RhD antigen were previously identified in alloimmunized donors and we have shown that instillation of these immunodominant RhD‐specific peptides to the nasal mucosa of DR transgenic mice prevents antibody responses to RhD protein. We now wished to test whether such tolerance can be effective in switching off antibody responses in mice that have already been immunized and also the mechanism by which tolerance is achieved. DR15 transgenic mice were immunized and boosted with purified RhD protein, and the immunodominant RhD peptides given nasally, either singly or in a mixture, 4 weeks later. This treatment was found to abrogate helper T cell responses of splenocytes stimulated with RhD protein in culture. This loss in splenocyte activity was often accompanied by an increase in IL‐10 production suggesting the presence of regulatory T cells. In addition, we have demonstrated that antibody levels in the serum declined more quickly in mice that had received the peptides. Thus, nasal instillation of immunodominant peptides provides a method by which to reverse established immune responses to red cells, and this approach may be effective in reducing anti‐D titres in alloimmunized women who are at risk of HDN.