Reversal of immunosuppression inducible through ultraviolet-exposed skin by in vivo anti-CD11b treatment.
In both human in vitro models and murine in vivo adoptive transfer studies, UV-induced class II MHC+ CD11b+ leukocytes that infiltrate the epidermis appear to mediate UV-induced immunosuppression. In the present study, their role is further probed using an anti-CD11b mAb (clone 5C6), which is effective in vivo in blocking CD11b+ monocyte/macrophage diapedesis into inflammatory lesions. A single exposure, low dose UV protocol (72 mJ/cm2) that resulted in tolerance only when dinitroflurobenzene was applied 48 h later through the UV-irradiated skin, but not through a distant non-UV-irradiated site, was used. In vivo anti-CD11b treatment in non-UV-irradiated mice did not block contact sensitivity responses. However, the ability to induce a primary contact sensitivity response was completely restored in UV-irradiated mice receiving anti-CD11b. This restoration was associated with partial restoration of papillary dermal class II MHC+ NLDC-145- cells. In vivo anti-CD11b treatment also blocked tolerance induction, which was associated with a 50% reduction in the infiltration of class II MHC+ CD11b+ Gr-1+ monocyte/macrophages into UV-irradiated skin. In addition, anti-CD11b treatment partially protected against epidermal UV injury, in that the epidermal structure was better preserved and the keratinocytes were less severely damaged. CD11b+ leukocytes may thus affect UV-irradiated skin through at least two mechanisms: 1) a class II MHC+ CD11b+ Gr-1+ monocyte/macrophage population inducing a state of tolerance to Ag(s) acquired in UV-irradiated skin, and 2) CD11b+ leukocytes capable of inflicting additional injury to both keratinocytes and constitutive APC damaged by UV photons.
Hammerberg
C
C
Department of Dermatology, University of Michigan, Ann Arbor 48109, USA.
Duraiswamy
N
N
Cooper
K D
KD
D000818:Animals; D000938:Antigen-Presenting Cells / Q000528:radiation effects; D003713:Dendritic Cells / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007111:Immunity, Cellular / Q000528:radiation effects; D007165:Immunosuppression Therapy; D016177:Macrophage-1 Antigen / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D012867:Skin / Q000276:immunology* / Q000528:radiation effects; D014466:Ultraviolet Rays
D000949:Histocompatibility Antigens Class II; D016177:Macrophage-1 Antigen