Mechanisms of Action of Thymoglobulin

Abstract

Thymoglobulin (Genzyme Transplant, Cambridge, MA) is a polyclonal rabbit anti-thymocyte globulin that consists of a mixture of different antibody specificities that interact with immune response antigens, adhesion molecules, cell-trafficking molecules, and a variety of other antigens involved in heterogeneous pathways. Thymoglobulin acts as a rapid T-cell depleting agent, primarily through complement-dependent cell lysis in the blood compartment and apoptotic cell death in lymphoid tissues. Although the primary immunosuppressive effect is T-cell depletion, Thymoglobulin has also been shown to modulate cell surface markers, including a number of integrins and intercellular adhesion molecules that facilitate leukocyte adhesion to the endothelium. Treatment with Thymoglobulin has been shown to be associated with both short- and long-term changes in T-cell populations, generating altered homeostasis characterized by expansion of specific T-cell subsets that have been shown to exhibit regulatory suppressor functions. Further exploration of the mechanisms of action of Thymoglobulin will be important to guiding therapy with this widely used agent in the transplant setting, as well as in emerging therapeutic areas.