Role of antigen-presenting cells in the development and persistence of contact hypersensitivity.

Abstract

Three outcomes pertinent to contact sensitivity (CS) [in mice] follow immunization with various forms of trinitrophenylated (TNP) substrates. Specific immunological unresponsiveness for CS is induced when immunization favors activation of splenic suppressor cells. This state is achieved by i.v. injection of TNP-conjugated to various types of cells, such as peritoneal exudate cells (PEC). A short-lived or evanescent form of CS is induced when immunization reduces activation of the suppressor circuit. This can be achieved by s.c. immunization with trinitrophenyl conjugated to syngeneic PEC, by pretreatment with cyclophosphamide to diminish suppression before i.v. immunization or by altering the mode of antigen presentation by using TNP-substrate that has undergone phagocytosis. A long-lived form of CS is induced when TNP is presented to the immune system or skin cells either by contact skin painting with reactive TNP, by s.c. or i.v. injection of TNP-conjugated epidermal cells. TNP-conjugated epidermal cells induced CS even when the suppressor circuit was activated by i.v. coadministration of TNP-PEC. This implies that antigen presentation or epidermal cells induces sensitized cells that are relatively resistant to suppression. The cell type(s) in the skin that are primarily responsible for this potent form of antigen presentation are most likely Langerhans cells, because they can be concentrated by virtue of their Fc receptors and they are Ia [immune response-associated antigen] positive. The anatomical site where antigen is first encountered by the immune apparatus and the nature of the cells which present the antigen determine whether a CS response will ensue, as well as whether it will be evanescent or long-lasting.