An anti-CD2 mAb induces immunosuppression and hyporesponsiveness of CD2⁺ human T cells in vitro

Abstract

We describe here the potent specific immunosuppression obtained in vitro by LO-CD2a, a rat mAb directed against the human CD2 molecule. Addition of low dose LO-CD2a (40 ng/ml) at the time of mixed lymphocyte culture (MLC) initiation inhibits 80% of the proliferation and, more impressive, addition of the mAb 4 days after culture initiation at a similar concentration still suppresses 50% of the MLC. When responder T cells previously treated with LO-CD2a are challenged a second time by the same donor or third party allogeneic cells, hyporesponsiveness occurs in both cases, although reactivity to T cell mitogenic stimulation persists. Finally, the low production of cytokines such as tumor necrosis factor-alpha and IFN-gamma after incubation of human T cells with LO-CD2a suggests the absence of T cell activation. These results demonstrate that LO-CD2a mAb has a significant immunosuppressive effect and induces hyporesponsiveness in vitro, thereby suggesting potential efficacy in vivo for the treatment of acute rejection and for the induction of tolerance in allotransplantation.

Effective therapy for a murine model of adult T-cell leukemia with the humanized anti-CD2 monoclonal antibody, MEDI-507

“…The limited expression of CD2 that is restricted to mature T cells and T-leukemic cells including MET-1 leukemic cells provides the scientific rationale for its use in antibody-mediated immunotherapy of ATL. MEDI-507 is a humanized mAb directed against CD2 that was genetically engineered from the rat version of the mAb (BTI-322) by BioTransplant (Charlestown, MA) for use in the prevention of allograft rejection [15][16][17] and in the therapy of graftversus-host disease (GVHD) and autoimmune diseases. 18 MEDI-507 (siplizumab) has been used in a series of phase 1 trials involving patients with psoriasis or with GVHD.…”

Alefacept reduces infiltrating T cells, activated dendritic cells, and inflammatory genes in psoriasis vulgaris

“…Despite identification of CD2 (E-rosette receptor) as the first stimulatory͞costimulatory T cell surface protein (17,18), surprisingly little is known about its regulatory function. Depending on the way CD2 is ligated, it can deliver a stimulatory or inhibitory signal or be involved in lymphocyte adhesion (19)(20)(21)(22)(23).…”

Novel Insight into the Agonistic Mechanism of Alefacept In Vivo: Differentially Expressed Genes May Serve as Biomarkers of Response in Psoriasis Patients

“…Mouse T cells do express CD2, but the binding interaction is with CD48, a molecule that has much lower affinity for CD2 compared with CD58. Even so, Abs to CD2 in murine models of transplantation or inflammation have been used successfully to attenuate T cell-mediated effector responses (6,7).…”