Activated complement component 3 (C3) is required for ultraviolet induction of immunosuppression and antigenic tolerance.
Complement component 3 (C3), a critical regulator of innate immunity, may also play a role in the regulation of cognate immunity, such as contact sensitivity responses. Because ultraviolet (UV) radiation also activates C3 in the skin, we determined whether the immunosuppressed state that results when a contact sensitizer is applied through UVB-exposed skin requires the presence and activation of C3. This question was addressed through the use of C3-deficient mice, blockade of C3 cleavage to C3b, and accelerated degradation of iC3b by soluble complement receptor 1 (sCR1). Both C3-modulated systems totally reversed the failure to induce a contact sensitivity response to dinitrofluorobenzene (DNFB) upon primary sensitization at the UV-exposed site, as well as immunologic tolerance to a second DNFB immunization through normal skin. Treatment with sCR1 reduced the infiltration of CD11b+ leukocytes into the epidermis and dermis of UV-irradiated skin but did not reverse the UV-induced depletion of epidermal class II MHC+CD11blo Langerhans cells. These data, taken together with previous results showing abrogation of locally induced UV immunosuppression by in vivo anti-CD11b treatment, suggest a novel mechanism by which ligation of the leukocyte beta2 integrin, CD11b, by iC3b molecules formed from C3 activation in UV-exposed skin, modifies cutaneous CD11b+ cells such that skin antigen-presenting cells are unable to sensitize in a primary immune response, but actively induce antigenic tolerance.
Hammerberg
C
C
Department of Dermatology, Case Western Reserve University, and University Hospitals of Cleveland, Cleveland, Ohio 44106, USA.
Katiyar
S K
SK
Carroll
M C
MC
Cooper
K D
KD
D000818:Animals; D000941:Antigens / Q000276:immunology*; D003176:Complement C3 / Q000172:deficiency / Q000378:metabolism*; D004139:Dinitrofluorobenzene / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D007165:Immunosuppression Therapy; D007962:Leukocytes / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000276:immunology; D051379:Mice; D010787:Photosensitivity Disorders / Q000276:immunology; D017463:Receptors, Complement 3b / Q000378:metabolism; D012879:Skin Physiological Phenomena / Q000276:immunology; D014466:Ultraviolet Rays
D000941:Antigens; D003176:Complement C3; D000949:Histocompatibility Antigens Class II; D016177:Macrophage-1 Antigen; D017463:Receptors, Complement 3b; D004139:Dinitrofluorobenzene