Mechanism of UVB-induced suppression of the immune response to Mycobacterium bovis bacillus Calmette-Guerin: role of cytokines on macrophage function.
Previously we demonstrated that treatment of mice with either UVB radiation or supernatants derived from UVB-irradiated PAM 212 keratinocytes decreased the induction of the delayed-type hypersensitivity (DTH) response to Mycobacterium bovis bacillus Calmette-Guerin (BCG), impaired the clearance of bacteria from their lymphoid organs and also altered macrophage functions. In order to characterize the cytokines involved in these phenomena, UV-irradiated mice were injected with antibodies to interleukin-10 (IL-10), transforming growth factor-beta 1 (TGF-beta 1), or tumor necrosis factor-alpha (TNF-alpha). Injection of UVB-irradiated mice with anti-IL-10 immediately after UV irradiation restored the DTH response and reversed the UV-induced inhibition of bacterial clearance. Injection of UV-irradiated mice with anti-TGF-beta only partially restored the DTH response although it allowed a better clearance of BCG than injection of mice with the control antibody. In contrast, injection of anti-TNF-alpha did not affect the UVB-induced suppression of DTH or impaired bacterial clearance. Similarly, the ability of macrophages to phagocytose BCG and kill the intracellular organisms was restored to almost normal levels after injecting UV-irradiated mice with antibodies specific for IL-10 or TGF-beta. Injection of mice with either recombinant IL-10 or TGF-beta mimicked the effect of whole-body UV irradiation on immune function. These results suggest that IL-10 has a major role in UV-induced suppression of both DTH to BCG and impairment in the clearance of bacteria and that TGF-beta has a more significant role in blocking bacterial clearance. Furthermore, these cytokines seem to modulate immune responses by altering macrophage functions in UVB-irradiated mice.
Jeevan
A
A
Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Ullrich
S E
SE
De Gracia
M
M
Shah
R
R
Sun
Y
Y
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D016207:Cytokines / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance / Q000528:radiation effects*; D008264:Macrophages / Q000276:immunology* / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000276:immunology*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D000907:Antibodies, Bacterial; D016207:Cytokines