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(Journal of Leukocyte Biology. 2000;68:633-640.)
© 2000 by Society for Leukocyte Biology

Tacrolimus (FK506) treatment of CD34⁺ hematopoietic progenitor cells promote the development of dendritic cells that drive CD4⁺ T cells toward Th2 responses

Kanako Shimizu^*,, Shin-ichiro Fujii^,, Koji Fujimoto, Keisei Kawa, Akira Yamada^* and Fumio Kawano

^* Department of Immunology, Kurume University School of Medicine, Fukuoka, Japan;
The Center for Bone Marrow Transplantation and Immunotherapy, Institute for Clinical Research, Kumamoto National Hospital, Kumamoto, Japan;
Department of Surgery, Biological Therapeutic Program, University of Pittsburgh School of Medicine, and University of Pittsburgh Cancer Institute, Pennsylvania; and
Department of Pediatrics, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan

Correspondence: Dr. Shin-ichiro Fujii, Laboratory of Cellular Physiology and Immunology, The Rockefeller University, 1230 York Ave., New York, NY 10021-6399. E-mail: fujii1018{at}aol.com

The macrolide lactone, tacrolimus (FK506), is utilized in bone marrow transplantation (BMT) to prevent graft-versus-host disease (GVHD). In the current study, we evaluated the ability of FK506 to modify the function of dendritic cells (DCs) derived from CD34⁺ hematopoietic progenitor cells (HPCs). Comparable to DCs obtained in the absence of FK506, DCs cultured in the presence of FK506 (FK-DCs) had higher expression of CD1a⁺ and formed a greater number of DC colonies. Despite the same expression of costimulatory molecules, FK-DCs displayed a reduced capacity to stimulate an allogeneic T cell response, and showed significantly lower interleukin (IL)-12 production. While normal DCs pulsed with the exogenous antigen, keyhole limpet hemocyanin (KLH) induced specific Th1-like interferon-(IFN-) producing CD4⁺ T cell line, FK-DCs induced Th2-like interleukin-4 (IL-4) producing CD4⁺ T cell line. These data demonstrate the ability of FK506 to induce Th2-promoting function in developing DCs.

Key Words: hematopoietic progenitor cell • dendritic cell • tacrolimus (FK506) • Th2

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