CTLA-4: a negative regulator of autoimmune disease

Nitin J Karandikar; Carol L Vanderlugt; Theresa L Walunas; Stephen D Miller; Jeffrey A Bluestone

doi:10.1084/jem.184.2.783

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CTLA-4: a negative regulator of autoimmune disease

Journal article

Open access

Peer reviewed

CTLA-4: a negative regulator of autoimmune disease

Nitin J Karandikar, Carol L Vanderlugt, Theresa L Walunas, Stephen D Miller and Jeffrey A Bluestone

The Journal of experimental medicine, Vol.184(2), pp.783-788

08/01/1996

DOI: 10.1084/jem.184.2.783

PMCID: PMC2192746

PMID: 8760834

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https://doi.org/10.1084/jem.184.2.783View

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Abstract

CTLA-4, a CD28 homologue expressed on activated T cells, binds with high affinity to the CD28 ligands, B7-1 (CD80) and B7-2 (CD86). This study was designed to examine the role of CTLA-4 in regulating autoimmune disease. Murine relapsing-remitting experimental autoimmune encephalomyelitis (R-EAE) is a demyelinating disease mediated by PLP139-151-specific CD4+ T cells in SJL/J mice. Anti-CTLA-4 mAbs (or their F(ab) fragments) enhanced in vitro proliferation and pro-inflammatory cytokine production by PLP139-151-primed lymph node cells. Addition of either reagent to in vitro activation cultures potentiated the ability of T cells to adoptively transfer disease to naive recipients. In vivo administration of anti-CTLA-4 mAb to recipients of PLP139-151-specific T cells resulted in accelerated and exacerbated disease. Finally, anti-CTLA-4 treatment of mice during disease remission resulted in the exacerbation of relapses. Collectively, these results suggest that CTLA-4 mediates the downregulation of ongoing immune responses and plays a major role in regulating autoimmunity.

Amino Acid Sequence

Peptides - chemistry

Lymphocyte Activation

Peptides - immunology

Encephalomyelitis, Autoimmune, Experimental - immunology

Molecular Sequence Data

Mice, Inbred Strains

Antigens, Differentiation - physiology

Myelin Basic Protein - immunology

CTLA-4 Antigen

Animals

Abatacept

Immunoconjugates

Autoantigens - immunology

Myelin Basic Protein - chemistry

Immunization, Passive

Female

Mice

Interleukin-2 - biosynthesis

Interferon-gamma - biosynthesis

Antigens, CD

Details

Title: Subtitle: CTLA-4: a negative regulator of autoimmune disease
Creators: Nitin J Karandikar - Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA
Carol L Vanderlugt
Theresa L Walunas
Stephen D Miller
Jeffrey A Bluestone
Resource Type: Journal article
Publication Details: The Journal of experimental medicine, Vol.184(2), pp.783-788
Publisher: United States
DOI: 10.1084/jem.184.2.783
PMID: 8760834
PMCID: PMC2192746
ISSN: 0022-1007
eISSN: 1540-9538
Grant note: NS30871 / NINDS NIH HHS AI35294 / NIAID NIH HHS NS26543 / NINDS NIH HHS
Language: English
Date published: 08/01/1996
Academic Unit: Pathology
Record Identifier: 9984046815002771

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