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PMID: 7543139 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation.

The Journal of experimental medicine ·Vol. 182 ·No. 2 ·1995-08-01 ·Pages 459-65

Krummel MF, Allison JP

Abstract

The importance of the B7/CD28/CTLA-4 molecules has been established in studies of antigen-presenting cell-derived B7 and its interaction with the T cell costimulatory molecule CD28. CTLA-4, a T cell surface glycoprotein that is related to CD28, can also interact with B7-1 and B7-2. However, less is known about the function of CTLA-4, which is expressed at highest levels after activation. We have generated an antibody to CTLA-4 to investigate the consequences of engagement of this molecule in a carefully defined system using highly purified T cells. We show here that the presence of low levels of B7-2 on freshly explanted T cells can partially inhibit T cell proliferation, and this inhibition is mediated by interactions with CTLA-4. Cross-linking of CTLA-4 together with the TCR and CD28 strongly inhibits proliferation and IL-2 secretion by T cells. Finally, results show that CD28 and CTLA-4 deliver opposing signals that appear to be integrated by the T cell in determining the response to activation. These data strongly suggest that the outcome of T cell antigen receptor stimulation is regulated by CD28 costimulatory signals, as well as inhibitory signals derived from CTLA-4.

MeSH Terms
Abatacept Amino Acid Sequence Animals Antibodies, Monoclonal/immunology Antigens, CD Antigens, Differentiation/physiology B7-1 Antigen/physiology CD28 Antigens/physiology CD3 Complex/physiology CD4-Positive T-Lymphocytes/immunology CD8-Positive T-Lymphocytes/immunology CTLA-4 Antigen Immunoconjugates Lymphocyte Activation Lymphokines/biosynthesis Mice Mice, Inbred BALB C Molecular Sequence Data Signal Transduction
Chemicals
Antibodies, Monoclonal Antigens, CD Antigens, Differentiation B7-1 Antigen CD28 Antigens CD3 Complex CTLA-4 Antigen Ctla4 protein, mouse Immunoconjugates Lymphokines Abatacept
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Krummel M F
Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.
Allison J P
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.182.2.459
Published
1995-08-01
Pages
459-65
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192127
Subset
IM
Grants
NCI NIH HHS · CA09179 · United States
NCI NIH HHS · CA40041 · United States
Corrections
CommentIn
PMID: 7543133
External Links
PubMed source DOI: 10.1084/jem.182.2.459 PMC Full Text View journal details
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