[T lymphocyte activation induced by monoclonal anti-CD3 antibodies: physiopathology of cytokine release].
Anti-CD3 monoclonal antibodies are largely used as therapeutic agents in clinical transplantation. Constrating with their potent immunosuppressive activity anti-CD3 antibodies also transiently express T cell activating properties. In vitro they promote T cell mitogenesis and in vivo, the self-limited cytokine release (including TNF, IFN gamma, IL-2, IL-3, IL-6) observed following the first anti-CD3 injection, is responsible for an acute clinical syndrome. Clinical studies as well as the experimental data obtained in mice, confirmed that TNF plays a fundamental role in the anti-CD3 induced syndrome. The administration of anti-TNF monoclonal antibodies prior to the first anti-CD3 injection prevents the syndrome not only by blocking TNF bioactivity but also, by modulating the circulating levels of the other anti-CD3-induced cytokins. In particular, this model allowed the description of regulatory pathways existing between TNF and IFN gamma, which in turn regulate IL-3 and IL-6 release.
Chatenoud
L
L
INSERM U25, Hôpital Necker, Paris.
Bach
J F
JF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000008:administration & dosage; D016207:Cytokines / Q000378:metabolism*; D004334:Drug Administration Schedule; D006801:Humans; D066298:In Vitro Techniques; D016853:Muromonab-CD3 / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D016207:Cytokines; D016853:Muromonab-CD3; D014409:Tumor Necrosis Factor-alpha
Activation lymphocytaire T induite par les anticorps monoclonaux anti-CD3: physiopathologie du relargage de cytokines.