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

Olga Azhipa, Kei Kimizuka, Atsunori Nakao, Hideyoshi Toyokawa, Toyokazu Okuda, Joao Seda Neto, Sean M. Alber, Takashi Kaizu, Angus W. Thomson, Anthony J. Demetris, Noriko Murase

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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.

Original languageEnglish
Pages (from-to)199-209
Number of pages11
JournalClinical Immunology
Volume114
Issue number2
DOIs
Publication statusPublished - Feb 2005
Externally publishedYes

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Keywords

  • B cells
  • Donor dendritic cells
  • Tacrolimus

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Azhipa, O., Kimizuka, K., Nakao, A., Toyokawa, H., Okuda, T., Neto, J. S., Alber, S. M., Kaizu, T., Thomson, A. W., Demetris, A. J., & Murase, N. (2005). Comparative analysis of the fate of donor dendritic cells and B cells and their influence on alloreactive T cell responses under tacrolimus immunosuppression. Clinical Immunology, 114(2), 199-209. https://doi.org/10.1016/j.clim.2004.10.005