Administration of an anti-interleukin 2 receptor monoclonal antibody prolongs cardiac allograft survival in mice.

Abstract

The immune response to a vascularized allograft involves a complex series of events, including T cell activation. A critical marker of T cell activation is the acquisition of stereospecific membrane receptors for the lymphokine, interleukin 2 (IL-2) (1-4). While resting T cells lack IL-2 receptors, in vitro studies (5,6) indicate that essentially all lectin-or alloantigen-stimulated proliferating T cells express the IL-2 receptor. Moreover, the interaction of IL-2 with receptorbearing cells is required for the clonal expansion of activated T cells (1-13). Whereas engagement of the T cell receptor for antigen is the first step in T cell activation, the interaction of IL-2 with the newly expressed IL-2 receptor is a requisite step in the common pathway of activation of all T cells. The extension of these in vitro findings to the process of allograft rejection in vivo has not been extensively studied. IL-2 is necessary to reconstitute the acute rejection response in vivo in T cell-deprived rats (14). However, direct evidence in vivo that the IL-2 receptor is involved in allograft rejection has been lacking.The rat monoclonal antibody (mAb) M7/20 binds to the murine IL-2 receptor, as demonstrated by its capacity to bind activated but not resting T cells in flow cytometry experiments, to prevent IL-2-mediated DNA synthesis in an IL-2-dependent cytotoxic T lymphocyte cell line, to precipitate an N-glycosylated 58 kilodalton glycoprotein, and to competitively inhibit binding of radiolabelled IL-2 (15). As such, it offers an opportunity to direct immunosuppressive therapy selectively against IL-2 receptor-bearing cells during allograft rejection. In this report, we examine the effect of administration of M7/20 on survival of cardiac allografts in mice. Materials and MethodsAnimals. Inbred male mice, weighing 20-25 gm, of strains C57BL/10, B10.BR, and B10.AKM (The Jackson Laboratory, Bar Harbor, ME) were used throughout. These strains are completely mismatched for the H-2 locus, but share the same genetic background.Operative Technique. Vascularized, heterotopic heart allografts were performed as

A Multicenter, Prospective, Randomized, Double-Blind Trial of Basiliximab in Heart Transplantation

“…18 Preclinical studies have consistently shown that the administration of mAbs that target the IL-2 receptor prevents AR and prolongs vascularized heart allograft survival. 19,20 However, relatively few clinical studies have investigated the use of mAb induction therapy in heart transplantation, and the results of these studies have varied.…”

T Cells

“…The CD4 1 T cells that transferred tolerance expressed CD25, the IL-2 receptor-a (15). This created a paradox, because CD4 1 T cells activated to mediate rejection expressed CD25 (39), and their depletion with mAbs to CD25 reduced rejection in animals (40,41) and humans (42). We now know that depletion of CD25 1 T cells prevents induction of tolerance in transplant and autoimmunity.…”

Involvement of interleukin 2 receptors in conceptus-derived suppression of T and B cell proliferation in horses

“…The (Altman, 1990), these results indicate that HCS interferes with the initial steps of cell activation and does not affect the later events involved in proliferation. Postponing HCS treatment for 24 h appeared to allow the cells enough time to become activated by mitogen and to begin producing lymphokines (Weiss et al, 1987 (Kirkman et al, 1985) and a high IL-2 can terminate pregnancy in mice (Lala et al, 1990), IL-2 may play an integral role in allograft acceptance. Results from many studies have indicated that a relationship exists between conceptus or uterine derived suppressor factors and IL-2 production (Segerson, 1988;Saito et al, 1990;Segerson & Gunsett, 1990;Segerson & Libby, 1990).…”