A The purpose of this study is to immunologically characterize the first operationally tolerant intestinal transplant (ITx) patient known to date.

B Flow cytometry and rtPCR were used to generate an immunophenotype of ITx patients, utilizing peripheral blood and allograft samples. Matched cohorts were selected with similar demographics to the patient.

C We report on a 20 year-old male who is operationally tolerant from an isolated ITx following non-compliance discontinuation of all immunosuppressive medication for 2.5 years. The patient was transplanted in 2010 for pseudo-obstruction and the donor was a 17 year-old male with 5/6 mismatched antigens. Patient meets criteria for operational tolerance by undetectable immunosuppressive drug levels, absence of any symptoms and pristine graft pathology. Given recipient's history of GvHD at 6 months, we hypothesized that his tolerance was due to chimerism. However, his peripheral blood showed no evidence of donor chimerism thus suggesting a mechanism of peripheral tolerance. To further investigate, we characterized lymphocytes in the allograft and found 7.6% CD3+ T cells, which is lower than a control cohort of ITx patients with 12.3% and a rejection cohort with 27.8%. Similarly, he had 20% CCR6+ Th17 cells, which is lower than 24% in the stable cohort and 48% in the rejection cohort, corroborating a protolerant immunophenotype in the allograft. He did, however, have 70% CD3+ T cells in his peripheral blood which was similar to his matched cohort. Further analysis revealed that our tolerant patient had 54% naive CD4+ T cells in peripheral blood, which was much higher than the average 34.8% in his matched cohorts, who had correspondingly more memory T cells. We also found 6.7% CD25^highCD127^low T regulatory cells, which was comparable to the average 5.7% of his matched cohorts, confirming a functionally balanced T cell compartment. Interestingly, our patient was also found to have 18.3% NK cells in peripheral blood compared to an average 7.7% in his matched cohorts. The vast majority of his NK cells were dim CD56+; a population associated with operational tolerance in liver transplantation.

D Our study provides novel mechanistic insights into operational tolerance in ITx and may have strong clinical implications for immunomonitoring and tolerance trials in ITx.

CITATION INFORMATION: Houlihan B, Cha P, Cosentino C, Kaiser J, Shukla A, Hawksworth J, Matsumoto C, Fishbein T, Kroemer A. Operational Tolerance in Intestinal Transplantation: A Proven Possibility. Am J Transplant. 2017;17 (suppl 3).

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