Background: In the last decade a semi-direct pathway of alloimune response was described, in which dendritic cells (DC) of the recipient acquire MHC molecules from donor cells via exosome exchange and/or trogocytosis. These antigen acquisition pathways seem to be physiologically important in the regulation of the normal immune response, amplifying this response. Maternal-fetal microchimerism may benefit from the same amplification mechanism to increase tolerance to an allogeneic solid organ graft in the offspring. Objective: determine the nature of the subset of antigen-acquiring cells (AAC) in spleen and peripheral blood; and study the effect of NIMA-acquisition on the T cell mediated alloimmune response. Material and Methods: NIMAd-exposed b/b offspring were obtained from the breeding of B6 males (b/b) with BDF1 females (b/d). Peripheral blood mononuclear cells (PBMC) and splenocytes were screened for the expression of H2Kd using flow cytometry. The antibody YAe, specific for the complex of peptide EΑ52-67+AIb, was also used to assess the indirect pathway. An in vivo MLR was performed by retroocular injection of 20×106 CFSE-labeled CD4+ splenocytes from TEa mice into NIMAd exposed mice. Proliferation of TEa cells in spleen and lymph nodes was assessed by the CFSE dilution at 4d. Results: Strong expression of Kd was indicative of a b/d offspring. Mice negative for H2Kd were sometimes dimly positive, indicating antigen acquisition from a microchimeric source in a b/b animal. In the spleen the AAC were only myeloid DC (CD11c+ B220-) whereas both myeloid and plasmacytoid DC (CD11c+ B220- and CD11c+ B220+) expressed the YAe epitope. Importantly, mice that failed to acquire Kd still expressed the YAe epitope, indicating that indirect pathway was presented in all offspring. However, we observed proliferation in CFSE-labeled TEa cells only in NIMAd mice that lacked H2Kd acquisition by mDC. No proliferation at all (similar to B6 negative control) was observed in NIMAd mice positive for AAC, even though the TEa/YAe epitope was clearly present. Conclusions: The acquisition of allogeneic MHC molecules seems to mediate the tolerogenic effect of NIMA exposure in microchimeric F1 backcross mice. Since in mice lacking AAC, the TEa Tg T cells proliferated well, we conclude that the indirect pathway alone is immunogenic, whereas the semi-direct pathway induces anergy in CD4+ T cells specific to the acquired antigen. The mechanism of this phenomenon is still unclear.
To cite this abstract in AMA style:Bracamonte-Baran W, Zhou Y, Burlingham W. Tolerogenic Effect of Maternal Microchimerism Is Linked to Semi-Direct Pathway, The [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/tolerogenic-effect-of-maternal-microchimerism-is-linked-to-semi-direct-pathway-the/. Accessed December 5, 2020.
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