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

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-γ(IFN-γ) 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.