[Background] IT is an efficacious treatment for chronic intestinal failure. Recent advance of immunosuppressive regimens have decreased the rejection rate and improved patient survival. The precise mechanisms remain to be elucidated. MDSC is a potent immature myeloid cells suppressing antigen-specific T cell response. MDSC accumulate not only in cancer patients, but also in transplant patients. There is no report as to MDSC in IT.

[Methods] Fifteen IT recipients were enrolled between January 2015 and November 2015. All the recipients received induction therapy followed by maintenance tacrolimus and steroid. Blood samples, obtaining peripheral blood mononuclear cells (PBMC), were collected when allograft function was stable without rejection. Four healthy subjects (HS) were also enrolled. All the patients participating in this study gave informed consent. Flow cytometry was used to identify potent MDSC-phenotype with the following surface markers: CD33⁺CD11b⁺ in the population of the lineage (CD3, CD19, and CD56)^–HLA-DR^-/low (linDR^–). We also discriminate 4 subpopulations, CD14^–CD15^–, CD14⁺CD15^– (monocytic-MDSC), CD14⁺CD15⁺, CD14^–CD15⁺ (granulocytic MDSC).

[Results] The frequency of MDSC-phenotypic cells (Mean percentage ± SEM = 12.74 ± 2.948, n = 11) significantly increased in linDR^– population of PBMC in IT patients as compared with HS (1.25 ± 0.586, n = 4, p = 0.0394). Although there is no significant difference in the percentage of MDSC between in HS and pretransplant IT patients (3.983 ± 1.198, n = 7), the frequency of MDSC-phenotypic cells significantly increased within 3 months after IT (10.35 ± 2.396, n = 4) as compared with those of HS and pretransplant IT patients (p = 0.0214). In the analysis of the subpopulation, the frequency of granulocytic-MDSC significantly increased as compared with those of HS (10.51 ± 2.313, n = 11 vs 1.02 ± 0.598, n = 4, p = 0.032) or pretransplant samples (1.801 ± 0.532, n = 7, p = 0.032) , but not those of other subpopulations. Functional study using anti-CD3/CD28-stimulating antibody reveals that lineage^–CD33⁺ MDSC suppressed proliferation of purified autologous naïve T cells and MDSC-depleted T cells.

[Conclusion] MDSC accumulate in IT patients from early phase after IT and might play a role in modulating recipient immune system.

CITATION INFORMATION: Okano S, Hashimoto K, Abu-Elmagd K, Fung J, Kish D, Keslar K, Min B, Fairchild R, Miller C. Myeloid-Derived Suppressor Cells (MDSC) Accumulate in Intestinal Transplant (IT) Patients. Am J Transplant. 2016;16 (suppl 3).

« Back to 2016 American Transplant Congress