Background: The development of MHC-specific IgE has been has been observed in various murine transplant models and highly sensitized transplant patients. The importance of IgE in allergies and other TH2 type illnesses has been extensively documented. However, little is known about this antibody isotype's possible involvement in transplant rejection. In addition to the effector mechanisms mediated through its high affinity receptor (FceRI) on mast cells and basophils, IgE also increases allergen-specific T cell activation. This effect is mediated through IgE-antigen immune complexes that bind to the low affinity receptor CD23 (FceRII) expressed on B cells, a process called facilitated antigen presentation (FAP). In this study, we explore whether MHC-specific IgE enhances alloresponses through CD23 in a manner akin to its role in allergy-related mechanisms.
Methods: Serum was isolated from sensitized C57BL/6 mice after rejection of a BALB/c cardiac allograft. The presence of MHC-specific IgE was confirmed employing an MHC-specific ELISA. Serum containing MHC-specific IgE (and control serum from which IgE was removed) was incubated with MHC-monomers to allow for formation of IgE-antigen immune complexes and subsequently injected in footpads of naïve C57BL/6 mice. C57BL/6 mice were or were not treated with anti-CD23. 7 days thereafter, draining lymph nodes were harvested and T cell activation was analyzed using Flow Cytometry. Changes in donor-reactive B cells were analyzed by staining with fluorophore-labelled MHC I and MHC II tetramers. 
Results: The injection of serum containing MHC-specific IgE together with MHC monomers leads to increased proliferation and activation of CD4 and CD8 T cells, as measured by Ki-67 and CD44 in the draining lymph node. Injection of serum without IgE had no such effect. This indicates a possible role of MHC-specific IgE in allospecific immunity.  To further investigate, if MHC-specific IgE specifically acts by binding to its receptor CD23 in combination with its cognate antigen, and therefore through FAP, CD23 was systemically blocked in a similar footpad injection model. Anti-CD23 decreased proliferation of CD8+ cells with statistical significance and showed a strong trend towards decrease proliferation of CD4+ cells. Furthermore, it reduced numbers of activated CD4+ and CD8+ T cells. Of note, both CD23 blocking and IgE removal reduced the number of MHC-reactive germinal center B lymphocytes, further indicating a role of MHC-specific IgE in alloreactivity.
Conclusion: These results suggest that donor-specific IgE increases alloreactivity through the binding of MHC-IgE complexes to CD23. Therefore, donor-specific IgE might play a role in the alloresponse.