Comparative analysis of the fate of donor dendritic cells and B cells and their influence on alloreactive T cell responses under tacrolimus immunosuppression.
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.
Azhipa
Olga
O
Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, 200 Lothrop Street, Pittsburgh, PA 15261, USA.
Kimizuka
Kei
K
Nakao
Atsunori
A
Toyokawa
Hideyoshi
H
Okuda
Toyokazu
T
Neto
Joao Seda
JS
Alber
Sean M
SM
Kaizu
Takashi
T
Thomson
Angus W
AW
Demetris
Anthony J
AJ
Murase
Noriko
N
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*
D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D016559:Tacrolimus