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 stu dies, UV-induced class II MHC(+)CD11b(+) leukocytes that infiltrate th e epidermis appear to mediate UV-induced immunosuppression. In the pre sent study, their role is further probed using an anti-CD11b mAb (clon e 5C6), which is effective in vivo in blocking CD11b(+) monocyte/macro phage diapedesis into inflammatory lesions, A single exposure, low dos e UV protocol (72 mJ/cm(2)) that resulted in tolerance only when dinit roflurobenzene was applied 48 h later through the UV-irradiated skin, but not through a distant non-UV-irradiated site, was used, In vivo an ti-CD11b treatment in non-UV-irradiated mice did not block contact sen sitivity responses, However, the ability to induce a primary contact s ensitivity response was completely restored in UV-irradiated mice rece iving anti-CD11b, This restoration was associated with partial restora tion of papillary dermal class II MHC(+) NLDC-145(-) cells, In vivo an ti-CD11b treatment also blocked tolerance induction, which was associa ted with a 50% reduction in the infiltration of class II MHC(+)CD11b()Gr-1(+) monocyte/macrophages into UV-irradiated skin, In addition, an ti-CD11b treatment partially protected against epidermal UV injury, in that the epidermal structure was better preserved and the keratinocyt es were less severely damaged, CD11b(+) leukocytes may thus affect UV- irradiated skin through at least two mechanisms: 1) a class II MHC(+)C D11b(+)Gr-1(+) monocyte/macrophage population inducing a state of tole rance to Ag(s) acquired in UV-irradiated skin, and 2) CD11b(+) leukocy tes capable of inflicting additional injury to both keratinocytes and constitutive APC damaged by UV photons.