Induction of immune tolerance across major histocompatibility complex barrier by transfusion of ultraviolet B-irradiated immature dendritic cells

BACKGROUND: Transfusion of ultraviolet B (UVB)-irradiated peripheral blood mononuclear cells (PBMNCs) induces immunologic tolerance across the major histocompatibility complex (MHC) barrier in a murine model. It is necessary, however, to reduce contaminating platelets (PLTs) to a minimum. Ex vivo preparation of dendritic cells (DCs) offers an opportunity to rid the contaminating PLTs. The use of immature and mature DCs (iDCs and mDCs) with and without UVB irradiation for tolerance induction was therefore investigated. STUDY DESIGN AND METHODS: iDCs and mDCs were prepared by culture of Balb/c (H-2d) mouse marrow cells in the presence of granulocyte-macrophage-colony-stimulating factor and interleukin-4. Different dose schedules of iDCs were tested for tolerance induction in CBA (H-2k) mice. Tolerance induction by UVB-irradiated iDCs and mDCs was compared. Tolerance induction in two additional strains of mice (C3H and C57BL/6) was also studied. The induction of tolerance was tested by challenging transfusions of treated mice with PBMNCs from the donor strain. The induction of negative regulatory CD4+ T cells in tolerized mice was examined. RESULTS: Four weekly transfusions of 5 x 10(4) UVB-irradiated iDCs from Balb/c mice efficiently induced immune tolerance in CBA and C3H mice. iDCs and mDCs without UVB irradiation could not induce immune tolerance. Tolerance induced by transfusions of UVB-irradiated iDCs was associated with the development of CD4+-regulatory T cells as demonstrated by an adoptive transfer study. CONCLUSION: Transfusion of UVB-iDCs induces immune tolerance across the MHC barrier in certain combinations of mouse strains. The results support the idea that iDCs irradiated with UVB may be applied to induce immune tolerance across the MHC barrier.