Exposure of C57BL/6 mice to UVR (8 kJ/m2)
causes systemic immunosuppression that can last for over 4 weeks. We propose that UVR effects on dendritic cell precursors
in the bone marrow are one mechanism of inducing long-lasting UVR-induced
systemic immunosuppression. Dendritic cells cultured from the bone marrow of
3-day post-irradiated (8 kJ/m2) BALB/c mice have a reduced capacity
to prime naïve T cells when adoptively transferred to naïve recipients. This UVR-induced
effect was maintained when bone marrow cells were cultured in GM-CSF and IL-4,
or FLT3L; culture conditions that produced dendritic cells with confirmed
different phenotypes. To investigate the function of dendritic cells generated in vivo from the bone marrow of
UV-irradiated mice, mouse chimeras were established. After 16 weeks, mice reconstituted
with bone marrow from UV-irradiated mice (UV-chimeric) had a reduced contact
hypersensitivity response compared to mice reconstituted with normal bone
marrow (control-chimeric). In addition, when the dorsal skin of UV-chimeric
mice were treated with either FITC or an erythemal dose of UVR (2 kJ/m2),
there were reduced cell yields in the draining lymph nodes at 24 h. In FITC
painted mice, the reduced cell yield corresponded with decreased FITC+
dendritic cells in the draining lymph nodes which were identified as migratory dermal
dendritic cells. Furthermore, when the bone marrow of UV-chimeric mice was
cultured for dendritic cell development, the cells had reduced priming ability.
These reduced functional responses in UV-chimeric mice were not due to
different numerical or proportional reconstitution of bone marrow or the
leukocyte populations in secondary lymphoid organs when compared with
control-chimeric mice. Our results suggest that UVR imprints a long-lasting
effect on dendritic cell precursors in the bone marrow and reduces the function
of the dendritic cells that are differentiated from these precursors. These findings
demonstrate a mechanism not previously associated with UVR-induced systemic
immunosuppression.