*Purpose: Treg-rich organized lymphoid structures (TOLS) has been identified in recipients with renal allograft tolerance induced by transient mixed chimerism in non-human primates (NHPs) and humans. To further clarify its relevance to tolerance, detailed immunological profiles in renal allografts were compared with those in chronic antibody-mediated rejection (CAMR) and T cell mediated rejection (TCMR) in NHPs.

*Methods: Using the NanoString nCounter platform, we retrospectively studied 53 mRNAs in 256 kidney allograft formalin-fixed paraffin-embedded serial samples taken from NHP recipients of combined kidney and bone marrow transplantation that achieved tolerance (TOL), developed CAMR or TCMR.

*Results: TOL recipients (n=14) survived for >1736 ± 454 days with normal kidney function, while recipients with CAMR (n=13) survived for 899 ± 152 days with compromised graft function and recipients with TCMR (n=15) survived only shortly (130 ± 17 days) (Fig. 1A). Most prominent difference observed among three groups was FOXP3, which was significantly higher in TOL than both CAMR and TCMR in both early (one year) after transplantation. Other mRNAs potentially related to Tregs, such as IL10, TGFβ and GATA3 were also high in TOL. In contrast, transcripts of inflammatory cytokines (IFNG, CXCL11, FCGR3A, GNLY, GZMB, IL4 and IL1RL1) were higher in TCMR, while activated endothelium associated transcripts, such as CAV1, MALL, VWF, TEK, ROBO4, SOX7 and PECAM1, were higher in CAMR (Fig. 1B).

*Conclusions: Significantly high FOXP3 and other Treg related mRNAs while suppressed inflammatory responses and endothelial activation may indicate critical importance of enriched Tregs in the allograft in the mechanism of renal allograft tolerance induced by transient mixed chimerism.

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