Immunosuppression in Vivo by a Soluble Form of the CTLA-4 T Cell Activation Molecule

In vitro, when the B7 molecule on the surface of antigen-presenting cells binds to the T cell surface molecules CD28 and CTLA-4, a costimulatory signal for T cell activation is generated. CTLA4Ig is a soluble form of the extracellular domain of CTLA-4 and binds B7 with high avidity. CTLA4Ig treatmen...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1992-08, Vol.257 (5071), p.792-795
Main Authors: Linsley, Peter S., Wallace, Philip M., Johnson, Jennifer, Gibson, Marylou G., Greene, JoAnne L., Ledbetter, Jeffrey A., Singh, Cherry, Tepper, Mark A.
Format: Article
Language:English
Subjects:
Abatacept
Animals
Antibody Formation - drug effects
Antigens, CD
Antigens, Differentiation - immunology
Antigens, Differentiation - metabolism
B lymphocytes
Biological and medical sciences
CHO Cells
Cricetinae
CTLA-4 Antigen
Erythrocytes - immunology
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Hemocyanins - immunology
Humans
Immune response
Immune response regulation
Immune tolerance
Immunization
Immunobiology
Immunoconjugates
Immunosuppression
Immunosuppressive Agents - pharmacokinetics
Immunosuppressive Agents - pharmacology
Intravenous injections
Lymphocyte Activation
Metabolic Clearance Rate
Mice
Mice, Inbred BALB C
Mice, Inbred Strains
Modulation of the immune response (stimulation, suppression)
Molecules
Recombinant Fusion Proteins - pharmacokinetics
Recombinant Fusion Proteins - pharmacology
Regulation
Spleen
Splenocytes
T cells
T lymphocytes
T-Lymphocytes - immunology
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Summary:In vitro, when the B7 molecule on the surface of antigen-presenting cells binds to the T cell surface molecules CD28 and CTLA-4, a costimulatory signal for T cell activation is generated. CTLA4Ig is a soluble form of the extracellular domain of CTLA-4 and binds B7 with high avidity. CTLA4Ig treatment in vivo suppressed T cell-dependent antibody responses to sheep erythrocytes or keyhole limpet hemocyanin. Large doses of CTLA4Ig suppressed responses to a second immunization. Thus, costimulation by B7 is important for humoral immune responses in vivo, and interference with costimulation may be useful for treatment of antibody-mediated autoimmune disease.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1496399