Blood, 15 August 2001, Vol. 98, No. 4, pp. 1239-1245
TRANSFUSION MEDICINE
Characterization of immunologic tolerance induced by
transfusion of UV-B-irradiated allogeneic mononuclear
leukocytes
Kuo-Jang Kao,
Eileen S. Huang, and
Sandra Donahue
From the Department of Pathology, Immunology and
Laboratory Medicine, University of Florida, Gainesville.
Transfusions of UV-B-irradiated peripheral blood mononuclear cells
(UV-B-PBMCs) from BALB/c (H-2d) mice into CBA
(H-2k) mice can induce humoral immune tolerance to
H-2d 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.
