Effects of Chloroquine on Antigen-Presenting Functions of Epidermal Cells from Normal and Psoriatic Skin

Abstract

The lysosomotropic drug chloroquine has been added to cultures containing peripheral blood mononuclear cells (PBMC) and allogeneic antigen-presenting cells obtained from the epidermis of normal human skin or from skin of patients with psoriasis. We found that in the presence of chloroquine, the allostimulatory properties of freshly obtained, normal epidermal antigen-presenting cells (EAPC) were profoundly impaired. By contrast, normal EAPC (cultured for 72 h prior to exposure to alloreactive T cells), as well as fresh EAPC from psoriatic skin were not impaired by chloroquine. In fact, in some experiments, cultured EAPC and psoriatic EAPC in the presence of chloroquine displayed significantly enhanced abilities to activate allogeneic T cells. Moreover, chloroquine partially reversed the inhibitory effect of transforming growth factor-beta (TGF beta) on T-cell activation induced by cultured normal EAPC. Fresh normal EAPC, which are normally impervious to the effects of TGF beta, were not protected by TGF beta from chloroquine inhibition. We conclude that the addition of chloroquine to tissue culture medium unmasks important differences in antigen processing and presenting properties of fresh, normal EAPC, on the one hand, and cultured normal EAPC and psoriatic EAPC on the other. The ability of chloroquine to exaggerate the accessory cell function of the latter cells may relate to the capacity of this drug to cause the secretion of acid hydrolases into their immediate microenvironment. Moreover, the capacity of chloroquine to enhance the accessory cell functions of freshly obtained psoriatic EAPC emphasizes an abnormality that psoriatic cells in the epidermis constitutively express. We postulate that this abnormality may be related to the clinical observations that psoriatic skin lesions may be induced or aggravated by chloroquine therapy.