*Purpose: Intestinal transplantation (ITx) is arguably the most immunogenic and complex organ transplantation, often accompanied with high rates of allograft rejection (AR) and graft-versus-host disease (GVHD), and subsequently low graft and patient survival rates. Antigen-presenting cells (APCs) have been shown to play essential roles in regulating both T-cell-mediated AR and GVHD responses. However, the mechanisms that underlie these roles with respect to APC subsets in AR and GVHD in ITx are poorly understood. The aim of this study was to characterize different subsets of APCs in blood of patients with GVHD, AR, and stable grafts after ITx.

*Methods: We obtained peripheral blood lymphocytes from 10 patients with GVHD, 16 patients with acute rejection, and 17 stable patients (without any complications) after ITx at two timepoints, pre-transplant and at AR/GVHD episode. We stained for dendritic cells (DCs) and monocytes (CXCR1, CD11b, CD11c, CD16, HLA-DR, CD14, CD103, CD3, CD45, CD19). Data were analyzed using flow cytometry.

*Results: In GVHD patients, we found higher monocyte subsets, higher myeloid DCs and less plasmacytoid tolerogenic DCs (pDC). Specifically, we demonstrated more non-classical monocyte subsets (0.73% vs 0.32%, p = 0.1) compared to their controls already prior to ITx. We also showed significantly higher myeloid DCs (48.4% vs 17%, p=0.015) and less pDCs (2.1% vs 16.0%, p<0.01) in GVHD versus stable patients during GVHD episodes. In AR patients, we found more classical monocytes, more myeloid DCs and reduced pDCs. Specifically, our analysis showed that significantly increased myeloid DCs (39.6% vs 21.9%, p=0.037) were associated with reduced pDCs (3.7 vs 22.1%, p<0.001) in AR compared to stable patients. Moreover, we found significant increase of classical monocytes in rejection patients versus stable transplant patients during AR (4.9% vs 2.8%, p=0.03).

*Conclusions: Our data indicate that both GvHD and rejection in ITx are associated with reduced pDCs and increased proinflammatory myeloid DCs. In conjunction with T cell and B cell monitoring, a more robust characterization of distinct APC cell phenotypes may offer an adjunct for a non-invasive biomarker for detecting rejection and GVHD episodes in ITx in the future.

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