title: Regulatory T-cell activation among patients who displayed operational tolerance following intra-portal administration of donor-specific antigens in living donor liver transplantation.
abstract: Immunologic tolerance is the goal for all transplant surgeons. We have reported that repeated donor-specific antigen transfusion (DST) via the portal vein allowed rapid reduction of immunosuppressants with decreased acute cellular rejection episodes among living donor liver transplantations (LDLT). Moreover, we demonstrated that intraportal DST induced macrochimerism of donor type CD56+ T cells in the liver graft. We examined the impact of FoxP3+CD4+CD25+ T cells in recipients who acquired almost tolerance after LDLT with intraportal DST. We defined the amount of immunosuppressants administered less than one time per week as "almost tolerance" after LDLT, which occurred among 14% of DST patients after adult-to-adult LDLT. Two patients (4%) have gotten been we used from immunosuppressants more than 2 years after LDLT 4 years prior. We examined the impact of FoxP3+CD4+CD25+ T cells both in recipients with almost daily immunosuppressants and those who acquired almost tolerance. The proportion of FoxP3+/CD4+CD25+ T cells in the almost tolerance group was significantly higher than that in the almost daily immunosuppressant group (P<.05). The increased proportion of FoxP3+/CD4+CD25+ T cells significantly correlated with time after LRLT (y=0.0964x+42.02, R2=0.8854). Repeated intraportal DST may be a goot tool to induce immunologic tolerance after LDLT. Both donor type CD56+ T cells and FoxP3+/CD4+CD25+ T cells may act as important regulatory cells for tolerance. The period after LDLT is important for acquiring immunologic tolerance.
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. kanishok@med.niigata-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Chikako
authors.forename: H
authors.initials: H
authors.lastname: Oya
authors.forename: S
authors.initials: S
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Kokai
authors.forename: K
authors.initials: K
authors.lastname: Miura
authors.forename: K
authors.initials: K
authors.lastname: Hatakeyama
mesh_terms: D019002:CD56 Antigen / Q000378:metabolism; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007519:Isoantigens / Q000008:administration & dosage* / Q000276:immunology; D007564:Japan; D016031:Liver Transplantation / Q000276:immunology*; D019520:Living Donors; D008213:Lymphocyte Activation; D011169:Portal Vein; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors; D018183:Transplantation Chimera; D023001:Transplantation Tolerance; D016896:Treatment Outcome
chemical_list: D019002:CD56 Antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D007519:Isoantigens; C522918:NCAM1 protein, human