Ciclosporin Inhibits the Effector Function of the T Effector Cell of Delayed Type Hypersensitivity

Abstract

A substantial body of data demonstrates the immunosuppressive properties of the fungal metabolite cyclosporin A (CyA). Several T cell responses such as a mixed leukocyte reaction and lectin mitogenesis are blocked by this drug. It has been suggested that CyA inhibits the first stages of the T cell responses by suppressing the T cell stimulatory signals leading to activation and proliferation. It has been shown that CyA prevents the expression of receptors for T cell growth factor interleukin 2 [5] and in addition depresses the production of IL2 via a pathway involving inhibition of IL 1. The delayed type hypersensitivity reaction to various antigens is usually depressed by CyA, particularly if it is administered during the induction phase [2]. However, recent investigations have shown that in various in vivo delayed type hypersensitivity models cyclosporin A may even enhance the immune response, depending on the time of administration [6]. We have used contact sensitivity to 2,4dinitrofluorobenzene (DNFB) in mice as a model of delayed type hypersensitivity to study the effects of CyA on this reaction. By transferring T effector cells of delayed type hypersensitivity (TDH cells) to naive recipients we were able to show that CyA does not inhibit the induction of this T subpopulation but very efficently blocks its functional expression in the recipient animal. CyA may even enhance the immune response if a suppressive dose (antigen overload) of the contact sensitizer is applied to the skin.