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p72 high affinity receptors (FcγRI) for the Fc portion of IgG molecules on human peripheral blood monocytes mediate a variety of beneficial functions, but also have deleterious effects in certain clinical situations. In the present study, the photosensitizing porphyrins hematoporphyrin derivative and dihematoporphyrin ether (DHE), which are known to preferentially affect the cell membrane, were found to significantly inhibit binding of mouse IgG2a antibodies to the ligand binding site of FcγRI on human peripheral blood monocytes and the U937 human monocytic cell line. FcγRI receptors could be identified with a monoclonal antibody which recognizes an epitope distinct from the ligand binding site, indicating that photosensitization induced a structural alteration rather than loss of the receptor molecule from the cell surface. The effect of DHE and light appeared to be highly specific, since binding of monoclonal antibodies to other surface structures was not decreased. DHE plus light-induced modulation of FcγRI was found to be mediated by superoxide anions, since addition of a mimic of superoxide dismutase restored both binding of mouse IgG2a to FcγRI as well as human monocyte accessory cell function. These studies identify porphyrin photosensitization as a unique mechanism by which to selectively down-regulate FcγRI-mediated functions.

Superantigens, such as staphylococcal enterotoxin B (SEB), elicit a strong proliferative response in T cells when presented in the context of major histocompatibility complex (MHC) class II molecules. We observed a similar T-cell response, when MHC class II-negative epidermal cell lines were employed as antigen-presenting cells. Immunoprecipitation studies indicated that the ligand to which SEB bound had a molecular mass of 46 kDa. Radiolabeled SEB could be immunoprecipitated from isolated membrane proteins on the SCC13 epidermal cell line with a monoclonal antibody directed against the MHC class I molecule, and transfection of the K-562 cell line with MHC class I molecules showed a 75% increased SEB-binding capacity compared with the nontransfected MHC class I- and class II-negative counterpart. In functional studies, antibodies to the MHC class I molecule inhibited T-cell proliferation by at least 50%. From these studies, we conclude that MHC class I molecules on malignant squamous cell carcinomas serve as ligands for SEB, which, given the appropriate costimulatory signals, is sufficient to allow for superantigen-induced T-cell proliferation.

Acute, low dose ultraviolet B radiation of murine body wall skin followed by local application of DNFB produces a state of antigen-specific unresponsiveness. This state is maintained at least in part by an Lyt-1+ T cell that effects unresponsiveness by impairing the induction phase of contact hypersensitivity. The absence of suppressor cells capable of acting at the effector stage of immunity suggests that tolerogenic signals derived from the skin establish suppressor networks that are incomplete and perhaps different from networks that are induced by systemic administration of tolerogens. It is proposed that ultraviolet radiation produces its effects by impairing the antigen-presenting potential of resident Langerhans cells in whose absence hapten-derivatized keratinocytes (or their products) are able to deliver a tolerogenic signal.

Introduction and objectives:Photodynamic therapy (PDT) with verteporfin may be particularly well suited for patients with multiple low risk non‐melanoma skin cancers (NMSC) while providing good cosmetic outcomes as compared to standard treatments. The objectives of this study were to prospectively assess the tumor responses and cosmetic outcomes of verteporfin‐treated NMSC.

UVA‐1 has distinct immunological effects which has allowed it to be useful for a number of cutaneous diseases that have been relatively resistant to other treatment modalities. These include urticaria pigmentosa, morphea/scleroderma and T‐cell mediated diseases such as atopic dermatitis and cutaneous T‐cell lymphoma. Since chronic hand dermatitis is also mediated by T‐cells, we hypothesized that UVA‐ 1 would be an effective treatment for that disease as well. Five subjects with recalcitrant hand dermatitis caused by dyshidrosis and/or chronic irritancy were treated with a medium dose regimen of UVA‐ 1. This consisted of 15 treatments of 60 J/cm2UVA 1 over 3 weeks. Subjects received a total of 900 J/cm2. A clinical scoring parameter, Dyshidrotic Area and Seventy Index Score (DASI), was administered to subjects prior to and following the UVA‐ 1 treatment course. Clinical photographs were also taken. All subjects showed improvement in hand dermatitis as demonstrated by clinical photographs and the DASI score (13 ± 5.35 before treatment; 6.3 ± 4.50 after treatment). UVA‐ 1 is an effective and rapid acting treatment for chronic hand dermatitis.

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