CTLA-4 Blockade Enhances Clinical Disease and Cytokine Production during Experimental Allergic Encephalomyelitis

Peter J. Perrin*, Jairo H. Maldonado, Tiffany A. Davis, Carl H. June, Michael K. Racke, Thomas Davis

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

232 Scopus citations

Abstract

The B7 family of cell surface molecules expressed on APC provides accessory signals to T cells via either CD28 or CTLA-4. However, while CD28 transduces a costimulatory signal that is required for an optimal immune response, CTLA-4 transmits a negative signal. These studies use an anti-CTLA-4 mAb to directly address the role of this T cell surface molecule in experimental allergic encephalomyelitis (EAE). CTLA-4 regulation of disease was assessed during initial immune cell interactions and during the effector stage of the encephalitogenic immune response. The effects of anti-CTLA-4 treatment were schedule dependent. CTLA-4 blockade during the onset of clinical symptoms markedly exacerbated disease, enhancing mortality. Disease exacerbation was associated with enhanced production of the encephalitogenic cytokines TNF-α IFN-γ and IL-2. Hence, CTLA-4 regulates the intensity of the autoimmune response in EAE, attenuating inflammatory cytokine production and clinical disease manifestations.

Original languageEnglish
Pages (from-to)1333-1336
Number of pages4
JournalJournal of Immunology
Volume157
Issue number4
StatePublished - 15 Aug 1996

Fingerprint

Dive into the research topics of 'CTLA-4 Blockade Enhances Clinical Disease and Cytokine Production during Experimental Allergic Encephalomyelitis'. Together they form a unique fingerprint.

Cite this