title: Comparative analysis of the fate of donor dendritic cells and B cells and their influence on alloreactive T cell responses under tacrolimus immunosuppression.
abstract: We have shown that tacrolimus (TAC)-induced liver allograft acceptance is associated with migration and persistence of donor B cells and dendritic cells (DC). To clarify whether these MHC class II+ leukocytes have favorable roles in inducing tolerance, we analyzed recipient T cell reactions after allogeneic B or DC infusion. LEW rat B cells localized exclusively in BN host B cell follicles without any direct contact with host T cells. While few donor DC migrated to T cell areas and marginal zones, they were captured by host APC, suggesting that allogeneic MHC class II+ cells may induce immune reactions via the indirect pathway. Although DC-infused non-immunosuppressed recipients showed enhanced ex vivo anti-donor responses, persistent in vitro donor-specific hyporeactivity was seen equally with donor DC or B cell infusion under TAC. The results indicate that donor MHC class II+ APC are capable of regulating recipient immune reactions under TAC. Possible involvement of the indirect pathway of allorecognition is discussed.
authors.affiliation: Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15261, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Azhipa
authors.forename: Kei
authors.initials: K
authors.lastname: Kimizuka
authors.forename: Atsunori
authors.initials: A
authors.lastname: Nakao
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Toyokawa
authors.forename: Toyokazu
authors.initials: T
authors.lastname: Okuda
authors.forename: Joao Seda
authors.initials: JS
authors.lastname: Neto
authors.forename: Sean M
authors.initials: SM
authors.lastname: Alber
authors.forename: Takashi
authors.initials: T
authors.lastname: Kaizu
authors.forename: Angus W
authors.initials: AW
authors.lastname: Thomson
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Demetris
authors.forename: Noriko
authors.initials: N
authors.lastname: Murase
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D016027:Heart Transplantation / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013047:Specific Pathogen-Free Organisms; D016559:Tacrolimus / Q000494:pharmacology*
chemical_list: D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D016559:Tacrolimus