Thymoglobulin: Presence and Affect in the Central Lymphatic Compartment

Overview

This study proposes to examine the effect of TMG therapy upon the cellular elements within the central (bone marrow) and peripheral (lymph node) lymphoid compartments of humans. Briefly, bone marrow aspirates and lymph nodes will be obtained at the time of transplant, from renal transplant recipients receiving TMG induction therapy. For comparative purposes, peripheral blood samples will also be obtained. Lymphocytes from these compartments will be assessed for CD antigen expression, apoptosis, cytokine production following memory immune responses, and functional assays to assess potential regulatory T-cell (Treg) activity.

Polyclonal anti-thymocyte globulins are used with increasing frequency to induce immunosuppression in organ transplant recipients. Induction therapy is used for the majority of persons receiving kidney transplant. In 2004, 72% of patients that received a kidney transplant also received induction therapy. This number is up from 46% reported in 1995. Anti-Thymocyte Globulin is the most commonly used agent for induction therapy. It was used for 37% of kidney recipients in 2004, and its use appears to be increasing year over year. A prominent example of this class of drugs is Thymoglobulin(TMG), a purified, pasteurized gamma immune globulin, which is obtained by immunization of rabbits with human thymocytes. The resulting preparation contains polyclonal antibodies directed against multiple T-cell markers, including CD antigens, HLA, and homing receptors. Although the mechanism of action for the immunosuppressive effects of TMG has not been fully elucidated, there is evidence that complement-dependent cell lysis and depletion, cell-surface antigen modulation, blocking of adhesion molecules, and partial T-cell activation/anergy may play potential roles. Many of the effects of TMG are evident in the peripheral blood compartment, including a rapid decline in circulating T-cells. Non-human primate studies have demonstrated that TMG treatment leads to depletion of T-cells via apoptosis in peripheral lymphoid tissues (spleen and lymph nodes), but no studies have been conducted to assess the effect of TMG in the bone marrow, and no studies have examined the peripheral lymphoid tissue in humans receiving TMG therapy.