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.
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August 01 1996
CTLA-4: a negative regulator of autoimmune disease.
N J Karandikar,
N J Karandikar
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
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C L Vanderlugt,
C L Vanderlugt
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
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T L Walunas,
T L Walunas
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
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S D Miller,
S D Miller
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
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J A Bluestone
J A Bluestone
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
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N J Karandikar
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
C L Vanderlugt
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
T L Walunas
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
S D Miller
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
J A Bluestone
Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1996) 184 (2): 783–788.
Citation
N J Karandikar, C L Vanderlugt, T L Walunas, S D Miller, J A Bluestone; CTLA-4: a negative regulator of autoimmune disease.. J Exp Med 1 August 1996; 184 (2): 783–788. doi: https://doi.org/10.1084/jem.184.2.783
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