Introduction: Little is known about innate lymphoid cell (ILC) populations in the human gut, and the turnover of these cells and their subsets after transplantation has never been evaluated previously.

Methods: Intestinal samples were taken from 2 isolated intestine (ITx) and 2 multivisceral (MvTx) transplant recipients at time of any operative resection, such as stoma closure or revision. Recipient transplant types/ages/time after transplantation were ITx/27 years/375 days, ITx/4.5 years/322 days, MvTx/53 years/251 days, and MvTx/15 years/8 years. Mucosa was excised sharply and processed with solution containing EDTA to isolate intraepithelial cells followed by solution containing collagenase to isolate lamina propria cells. ILCs were analyzed by flow cytometry. The target population was defined as being negative for lineage markers (CD3, CD5, CD8, CD11b, CD19) and double-positive for CD45/CD127. Cells were further stained with cKit and CD56 to define ILC subsets and a donor-specific marker to analyze chimerism.

Results: Mean donor chimerism of ILCs was 23.4% (range 9.9-61.4%) at median follow up of 348.5 days with up to 10.3% remaining at 8 years compared to <1% donor T cells. Among recipient-derived ILCs, those expressing markers consistent with NK (type 1 ILCs with high CD56 and low cKit, which correspond with Th1 function) and NK22 cells (type 3 ILCs double-positive for CD56 and cKit, which correspond with Th17 function) predominated, while cells expressing markers consistent with LTi cells (another type 3 ILC positive for cKit but not CD56) predominated among remaining donor-derived ILCs. The percentage of donor LTi versus the overall percentage of donor ILC in the 4 patients was 84.6/61.4, 61.3/12.3, 23.1/9.6, and 17.9/10.3.

Discussion: This first report of ILC chimerism after intestinal and multivisceral transplantation shows persistence of donor ILCs up to 8 years after transplantation. Cells expressing LTi markers predominated among the donor ILCs, and cells expressing NK markers predominated among the recipient ILCs. Thus, donor ILCs appear to survive long-term after transplantation. Our data suggest that human LTi cells may form in the fetus and persist throughout life, as hypothesized in rodents.

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