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-PB MCs) from BALB/c (H-2(d)) mice into CBA (H-2(k)) mice can induce humoral im mune tolerance to H-2(d) antigens, and the induced tolerance is partially m ediated by negative regulatory PBMCs. To further identify which subset of s pleen mononuclear leukocytes (MNLs) in the tolerant CBA mice is responsible for the negative regulatory activity, adoptive transfer experiments were c onducted using spleen MNLs from the tolerant CBA mice. Results showed that only CD4(+) T cells could transfer the negative regulatory activity in a do se-dependent manner. This negative regulatory activity was significantly re duced when CD25(+) helper T cells were removed. Further study suggested tha t 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 productio n profile by CBA CD4(+) T cells, after stimulation with gamma-irradiated BA LB/c spleen cells, revealed an enhanced production of the type 2 T-cell cyt okines 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 media ted 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 mo nitor tolerance induction and the selection of gamma radiation dose is crit ical for potential clinical application of the tolerance induced by UV-B-PB MCs.