Antigen-presenting OKM5+ melanophages appear in human epidermis after ultraviolet radiation

Abstract

Ultraviolet radiation of murine skin in vivo or epidermal cells (EC) in vitro dramatically inhibits the antigen-presenting capacity of EC in vitro and results in the inhibition of immune responses to antigen challenge. In humans, UV exposure in vivo markedly inhibits alloantigen presentation by EC in the EC-lymphocyte reaction (ELR) when EC are harvested immediately after the administration of 4 times the minimal erythema dose (4 MED), whereas EC harvested 72 h after 4 MED (UV-EC) exhibit enhanced allostimulatory capacity in the ELR. This enhanced ELR reactivity is due to the appearance, in the epidermis, of bone marrow-derived OKT6- DR+ cells which are distinct from Langerhans cells (LC) in their lack of surface OKT6 and in their ultrastructural morphology. This report focuses on the phenotype and function of T6- Dr+ UV-EC and on their relationship to known human antigen presenting cell (APC) subsets. Approximately 60% of T6- Dr+ UV-EC bore the monocyte marker defined by monoclonal antibody OKM5, but lacked determinants recognized by OKM1, LeuM1, LeuM3, LeuM4, LeuM5, and Mac1. All T6- Dr+ UV-EC bore the class II MHC antigen HLA-DQ (DC/DS), which is associated with a specialized subset of antigen-presenting monocytes capable of stimulation in the autologous mixed leukocyte reaction (AMLR). Panning of OKM5+ UV-EC resulted in a population of cells which was markedly enriched in melanophages and which exhibited potent alloantigen-presenting capacity in the ELR. Since OKM5+ T6- Dr+ UV-EC were similar to the specialized APC minor subset of OKM1- OKM5+ blood monocytes both in phenotype and in apparent phagocytic function, we examined other APC functions of UV-EC to assess the extent of this analogy. Relative to control EC (containing only LC as APC), UV-EC (containing functionally inactivated LC but many T6-Dr+ APC) induced significantly greater degrees of T-cell proliferation in the presence of either tetanus toxoid antigen or the mitogen concanavalin A. UV-EC, as well as panning-purified OKM5+ UV-EC, were also able to induce autologous T-cell proliferation in the absence of added antigen (autologous ELR), in contrast to control EC which were poor stimulators of an autologous ELR. Thus, although human EC 72 h after UV exposure are numerically and functionally depleted of LC, at least 2 additional subsets of T6- Dr+ APC appear in the epidermis. One of these subsets is OKM1- OKM5- DQ+. The major subset is OKM1- OKM5+ DQ+ and appears phenotypically and functionally analogous to the highly specialized OKM1- OKM5+ subset of blood monocytes capable of phagocytosis, soluble antigen presentation, and stimulation in the AMLR. These non-LC APC subsets may be involved in altered APC-T cell activation mechanisms when skin is irradiated with UV in vivo. © 1986.