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, celltrafficking 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.

Rabbit antithymocyte globulin (Thymoglobulin(R)) impairs the thymic output of both conventional and regulatory CD4+ T cells after allogeneic hematopoietic stem cell transplantation in adult patients

“…In this study ATG-G was used, which contains a diverse spectrum of antibody specificities depleting various T-cell subsets. 17 Clinical data regarding the effect of ATG-G on thymopoiesis after allogeneic HSCT are scarce, and the effect of ATG-G on thymic output of regulatory T cells (Treg), in particular after allogeneic HSCT, has not been studied yet.…”

Rabbit Anti-Thymocyte Globulin: Evidence for Clinical Benefit in High Immunological Risk Kidney Transplantation

“…7 A full discussion of the known mechanisms of action of rATG is beyond the scope of this paper and the reader is referred to some excellent reviews. [7][8][9][10][11][12][13] A few important properties will be analyzed for this discussion. The primary effect of rATG is T cell inhibition and depletion through complement dependent cell lysis in the blood and apoptosis in the lymphoid tissue.…”

“…The primary effect of rATG is T cell inhibition and depletion through complement dependent cell lysis in the blood and apoptosis in the lymphoid tissue. [7][8][9] Modulation of T cell receptors leaves the T cell hypo-responsive to stimuli and also inhibits T cell homing. 7,14 This latter characteristic of inhibition of leukocyte adhesion via CD11a/LFA-1 in addition to blockade of leukocyte trafficking via T cell CXCR4/SDF-1α mediated chemotaxis may explain the decreased ischemiareperfusion injury leading to less delayed graft function compared to other antibody preparations.…”

Immunosuppressive Drug Therapy

“…Antithymocyte globulin (ATG) is produced by immunizing rabbits or horses with human thy- (Mueller 2007). The equine ATG (eATG) product ATGAM became available in the 1980s, whereas rabbit-ATG (rATG) or thymoglobulin was introduced commercially in 1999. rATG or eATG are used both as induction agents, especially in high-risk renal transplant recipients, and for the treatment of moderate to severe acute rejection.…”