PUVA therapy decreases HLA-DR+ CDIa+ Langerhans cells and epidermal cell antigen-presenting capacity in human skin, but flow cytometrically-sorted residual HLA-DR+ CDIa+ Langerhans cells exhibit normal alloantigen-presenting function

Abstract

We have investigated the effects of PUVA therapy on human Langerhans cell (LC) immunophenotype and function. Epidermal sheets were obtained from exposed, and control shielded, forearm skin at the end of a course of PUVA therapy, in patients receiving treatment routinely for a variety of dermatoses. PUVA therapy decreased the overall number of HLA-DR+CDIa+ LCs in epidermal sheets, and in epidermal cell (EC) suspensions examined using a fluorescence activated cell sorter (FACS). PUVA therapy also reduced the overall EC allostimulatory capacity in the allogeneic epidermal cell-lymphocyte reaction (ELR), and the capacity of ECs to present tetanus toxoid to, and augment concanavalin A-mediated stimulation of, lymphocytes in the autologous ELR. Depressed allostimulation by ECs from PUVA-treated skin could not be restored by indomethacin (added to block prostaglandin synthesis). The reductions in LC numbers and EC allostimulatory capacity varied according to dose, and time since cessation, of PUVA therapy, and in individual patients were of comparable degree. By contrast, the allostimulatory capacity of residual LCs from PUVA-treated skin (purified using the FACS) did not differ from that of purified control LCs. PUVA-induced suppression of cutaneous immune responses, therefore, results at least in part from an overall impairment of EC antigen-presenting capacity. Residual HLA-DR+CDIa+ LCs in PUVA-treated skin which retain their alloantigen-presenting function may represent a subgroup of PUVA-resistant LCs; alternatively, these cells may be as yet unaffected because they have only recently migrated into the epidermis.