Prevention of the humoral response induced by an anti-CD3 monoclonal antibody by deoxyspergualin in a murine model.
Multiple treatments with the potent immunosuppressant murine antihuman CD3 mAb OKT3 is sometimes precluded by the onset of a neutralizing humoral response mostly consisting of anti-idiotypic antibodies. A hamster antimurine CD3 monoclonal Ab, 145-2C11, shares many properties with OKT3, in particular the ability to induce a strong Ab response in mice. Deoxyspergulain (DSG), a metabolite of the antibiotic spergualin, has been shown to reduce Ab production triggered by pathogens in a variety of infectious models and against common antigens. In this study, we examined the ability of DSG to inhibit the humoral response induced by 145-2C11. DSG prevented the Ab production triggered by the anti-CD3 mAb in an Ag-specific manner and significantly reduced the Ab production in mice previously primed with 145-2C11. We showed that DSG had a long-term effect on B cells and a transient effect on T cells. In effect, DSG was found to induce a prolonged Ag-specific unresponsiveness of B lymphocytes, and to transiently reduce the capacity of T lymphocytes to deliver help to B cells, in part by reducing IL-4 production. DSG did not reduce the immunosuppressive properties of the anti-CD3 mAb. In fact, the combination of DSG with 145-2C11 prolonged the survival of allogeneic skin grafts when compared with the administration of 145-2C11 or DSG alone. Thus, the coadministration of DSG with OKT3 may be of clinical interest to reduce the humoral response triggered by the mAb.
Alegre
M L
ML
Department of Medicine, University of Chicago, Illnois 60637.
Sattar
H A
HA
Herold
K C
KC
Smith
J
J
Tepper
M A
MA
Bluestone
J A
JA
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D017252:CD3 Complex / Q000276:immunology; D006224:Cricetinae; D004797:Enzyme-Linked Immunosorbent Assay; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016853:Muromonab-CD3 / Q000494:pharmacology*; D051381:Rats; D016038:Skin Transplantation / Q000276:immunology*
D017252:CD3 Complex; D006146:Guanidines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; C037258:gusperimus