Characterization of immunologic tolerance induced by transfusion of UV-B--irradiated allogeneic mononuclear leukocytes.

Transfusions of UV-B--irradiated peripheral blood mononuclear cells (UV-B--PBMCs) from BALB/c (H-2(d)) mice into CBA (H-2(k)) mice can induce humoral immune tolerance to H-2(d) antigens, and the induced tolerance is partially mediated by negative regulatory PBMCs. To further identify which subset of spleen mononuclear leukocytes (MNLs) in the tolerant CBA mice is responsible for the negative regulatory activity, adoptive transfer experiments were conducted using spleen MNLs from the tolerant CBA mice. Results showed that only CD4(+) T cells could transfer the negative regulatory activity in a dose-dependent manner. This negative regulatory activity was significantly reduced when CD25(+) helper T cells were removed. Further study suggested that inhibition of IL-12 production by UV-B--irradiated PBMCs played a role in the induction of immune tolerance. In vitro study of the cytokine production profile by CBA CD4(+) T cells, after stimulation with gamma-irradiated BALB/c spleen cells, revealed an enhanced production of the type 2 T-cell cytokines after tolerance induction. Induction of tolerance also prevented the development of cytotoxic T cells in CBA mice against BALB/c MNLs. Adoptive transfer study suggested that the cellular immune tolerance was also mediated by CD4(+) negative regulatory T cells. The induced immune tolerance was nullified after 400 cGy sublethal gamma irradiation. These results suggest that the ex vivo study of cytokine production by T cells may be used to monitor tolerance induction and the selection of gamma radiation dose is critical for potential clinical application of the tolerance induced by UV-B--PBMCs. (Blood. 2001;98:1239-1245)