An anti-CD2 mAb induces immunosuppression and hyporesponsiveness of CD2+ human T cells in vitro.
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.
Latinne
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Transplantation Immunology Unit, Faculty of Medicine, University of Louvain Medical School, Clos Chapelle aux Champs 30, B-1200 Brussels, Belgium.
De La Parra
B
B
Nizet
Y
Y
Cornet
A
A
Giovino-Barry
V
V
Monroy
R L
RL
White-Scharf
M E
ME
Bazin
H
H
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018801:CD2 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D016853:Muromonab-CD3 / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; C105249:LO-CD2a; D016853:Muromonab-CD3; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma