CTLA-4

A negative regulator of autoimmune disease

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

Research output: Contribution to journalArticle

324 Citations (Scopus)

Abstract

CTLA-4, a CD28 homologue expressed on activated cells, binds with high affinity to the CD28 ligand, B and-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 PLP139-161-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 vitro administration of anti-CTLA-4 mAb to recipients of PLP139-151-specific 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.

Original languageEnglish (US)
Pages (from-to)783-788
Number of pages6
JournalJournal of Experimental Medicine
Volume184
Issue number2
StatePublished - Aug 1 1996

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Autoimmune Diseases
T-Lymphocytes
Autoimmune Experimental Encephalomyelitis
Demyelinating Diseases
Autoimmunity
Down-Regulation
Lymph Nodes
Cytokines
Ligands
Recurrence
In Vitro Techniques

ASJC Scopus subject areas

  • Immunology

Cite this

Karandikar, N. J., Vanderlugt, C. L., Walunas, T. L., Miller, S. D., & Bluestone, J. A. (1996). CTLA-4: A negative regulator of autoimmune disease. Journal of Experimental Medicine, 184(2), 783-788.

CTLA-4 : A negative regulator of autoimmune disease. / Karandikar, Nitin J.; Vanderlugt, Carol L.; Walunas, Theresa L.; Miller, Stephen D.; Bluestone, Jeffrey A.

In: Journal of Experimental Medicine, Vol. 184, No. 2, 01.08.1996, p. 783-788.

Research output: Contribution to journalArticle

Karandikar, NJ, Vanderlugt, CL, Walunas, TL, Miller, SD & Bluestone, JA 1996, 'CTLA-4: A negative regulator of autoimmune disease', Journal of Experimental Medicine, vol. 184, no. 2, pp. 783-788.
Karandikar NJ, Vanderlugt CL, Walunas TL, Miller SD, Bluestone JA. CTLA-4: A negative regulator of autoimmune disease. Journal of Experimental Medicine. 1996 Aug 1;184(2):783-788.
Karandikar, Nitin J. ; Vanderlugt, Carol L. ; Walunas, Theresa L. ; Miller, Stephen D. ; Bluestone, Jeffrey A. / CTLA-4 : A negative regulator of autoimmune disease. In: Journal of Experimental Medicine. 1996 ; Vol. 184, No. 2. pp. 783-788.
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