Cross dressing by donor dendritic cells maximizes T cell responses to indirectly presented alloantigen after BMT by promoting immune synapse formation (TRAN3P.903)

Abstract

Abstract The role of trogocytosis in generating naïve T cell responses is controversial and highly relevant to transplantation. We transplanted B6.CD11cGFP donor bone marrow (BM) grafts (H2Db, IAb, GFP off the CD11c promoter) into irradiated B6D2F1 (H2Db/d, IAb/d,) and tracked donor DC. Using standard and imaging flow cytometry, we noted that all donor cells become “cross-dressed” in high levels of recipient hematopoietic cell-derived MHC early after BMT. To assess the functional consequences of cross-dressed MHC, we transplanted B6.MHCII-/- BM into WT B6 recipients to generate DC cross-dressed with IAb. WT DC induced proliferation in BALB/c CD4 T cells transferred into B6.MHCII-/- recipients but no responses were seen to B6.MHCII-/- DC bearing cross-dressed Ag. Next, DC were generated that were either cross-dressed (B6.MHCII-/-→B6D2F1), bore cross-dressed and indirectly presented Ag (B6→B6D2F1), or could present indirect Ag only (B6→B6.MHCII-/-xD2F1) to the allospecific TEa Tg T cell. T cell proliferation was maximal in response to processed recipient alloAg presented via the indirect pathway in the presence of cross-dressed Ag, markedly reduced to indirect Ag when cross-dressing was absent, and absent to cross-dressed Ag alone. Imaging flow cytometry confirmed that cross-dressing promotes formation of the immunologic synapse. Thus, cross-dressing serves to maximize naïve T cell responses to indirectly presented alloAg and exerts this effect after BMT via the immunologic synapse.