Comparative analysis of the fate of donor dendritic cells and B cells and their influence on alloreactive T cell responses under tacrolimus immunosuppression

Clin Immunol. 2005 Feb;114(2):199-209. doi: 10.1016/j.clim.2004.10.005.

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • Dendritic Cells / immunology*
  • Flow Cytometry
  • Heart Transplantation / immunology
  • Histocompatibility Antigens Class II / immunology
  • Immune Tolerance / drug effects
  • Immune Tolerance / immunology
  • Immunohistochemistry
  • Immunosuppressive Agents / pharmacology*
  • Interferon-gamma
  • Lymphocyte Culture Test, Mixed
  • Male
  • Rats
  • Rats, Inbred BN
  • Rats, Inbred Lew
  • Specific Pathogen-Free Organisms
  • Tacrolimus / pharmacology*

Substances

  • Histocompatibility Antigens Class II
  • Immunosuppressive Agents
  • Interferon-gamma
  • Tacrolimus