Anti-CD4 and anti-CD2 monoclonal antibody infusions in subjects with multiple sclerosis. Immunosuppressive effects and human anti-mouse responses.
The immunologic responses to anti-T4 and anti-T11 mAb infusions were assessed in subjects with chronic progressive multiple sclerosis as part of phase I clinical studies. Eight subjects received five daily infusions (0.2 mg/kg/day) of either anti-T11 (CD2) or anti-T4 (CD4) murine mAb. It was found that in vivo anti-T cell mAb infusions specifically suppress in vitro measurements of the human immune response; anti-T11 mAb blocked T cell activation via the CD2 SRBC-binding protein, and anti-T4 mAb infusions abolished PWM-induced Ig synthesis without lysis of the CD4+ T cell subpopulations. With repeated infusions of the anti-T11 mAb in three subjects, anti-mouse antibodies were found in the circulation. Although the majority of human anti-mouse antibody was not isotype specific, significant anti-idiotypic-like activity was observed after repeated infusions in two of three subjects. The human anti-mouse antibodies were almost exclusively of the IgG isotype. The magnitude of the human anti-mouse response was significantly less after administration of either anti-T11 or anti-T4 as compared with anti-T12 mAb. Murine anti-T cell mAb can provide a specific, benign form of acute immunosuppression in humans. However, repeated administration of these reagents in more chronic diseases can result in anti-Id-like antibodies that block binding of the anti-T cell mAb to the T cell surface.
Hafler
D A
DA
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Ritz
J
J
Schlossman
S F
SF
Weiner
H L
HL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000918:Antibody Specificity; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000032:analysis; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D051379:Mice; D008807:Mice, Inbred BALB C; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology*; D010641:Phenotype; D012882:Skin Tests; D013601:T-Lymphocytes / Q000145:classification
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000939:Epitopes; D007132:Immunoglobulin Isotypes; D007166:Immunosuppressive Agents