Long-term inhibition of murine experimental autoimmune encephalomyelitis using CTLA-4-Fc supports a key role for CD28 costimulation

The Journal of Clinical Investigation
A H CrossR W Karr

Abstract

T cell activation involves not only recognition of antigen presented by the MHC, but also nonspecific interactions termed "costimulation." The costimulatory molecules B7-1 and B7-2 are ligands on antigen-presenting cells for the CD28 and CTLA-4 receptors on T cells. Previously, a fusion protein consisting of human CTLA-4 linked to human Fc was shown to bind B7-1 and B7-2 with high avidity and to prevent specific T cell activation. Here we investigated the effects of a recombinant fusion protein consisting of the extracellular domain of human CTLA-4 bound to mouse IgG2a Fc (CTLA-4-Fc) upon experimental autoimmune encephalomyelitis, a T cell-mediated disease that serves as a model for multiple sclerosis. CTLA-4-Fc prevented experimental autoimmune encephalomyelitis in 26 of 28 CTLA-4-Fc-treated mice (median maximum score 0), whereas 28 of 30 mice treated with control mouse IgG2a developed disease (median maximum score 2.75). Less inflammation and virtually no demyelination or axonal loss occurred in CTLA-4-Fc-treated compared with control-treated mice. Activated splenocytes from CTLA-4-Fc-treated mice were able to transfer disease adoptively to naive recipients. These results indicate a key role for the B7/CD28 system in the deve...Continue Reading

References

Dec 1, 1992·The Journal of Experimental Medicine·P S LinsleyN K Damle
Aug 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·C D GimmiL M Nadler
Sep 1, 1991·The Journal of Experimental Medicine·P S LinsleyJ A Ledbetter
Mar 1, 1991·The Journal of Clinical Investigation·K SelmajC F Brosnan
Feb 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·C B ThompsonC H June
Mar 1, 1989·Immunology Today·D A Hafler, H L Weiner
Aug 1, 1989·The Journal of Experimental Medicine·F M HofmanJ E Merrill
Apr 1, 1988·Annals of Neurology·K W Selmaj, C S Raine
Oct 1, 1973·Journal of Neurochemistry·W T Norton, S E Poduslo
Jul 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·P H SchreierD Baltimore
Aug 26, 1994·Science·B K FinckD Wofsy
Nov 4, 1993·Nature·M AzumaC Somoza
Oct 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·C G SagerströmM M Davis

❮ Previous
Next ❯

Citations

Nov 11, 1999·European Journal of Immunology·G MagistrelliY Delneste
Aug 30, 2012·Zeitschrift für Rheumatologie·A Rubbert-Roth, H-F Petereit
Aug 21, 2013·Trends in Immunology·Sabrina CeerazRandolph J Noelle
Oct 9, 2007·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Vissia Viglietta, Samia J Khoury
Jan 1, 2003·Journal of Neuroimmunology·Orhun H KantarciBrian G Weinshenker
Dec 1, 1996·Current Opinion in Immunology·E A TivolA H Sharpe
Apr 1, 1997·Current Opinion in Immunology·A Ashkenazi, S M Chamow
Mar 11, 1998·Current Opinion in Immunology·M Murakami, T Honjo
Oct 13, 2000·Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology·K Tamada, L Chen
Apr 29, 1998·Immunology and Cell Biology·D O Willenborg, M A Staykova
Mar 3, 2001·The New England Journal of Medicine·T Kamradt, N A Mitchison
Nov 17, 2001·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·M GiorelliM Trojano
Oct 1, 1996·Immunological Reviews·C A ChambersJ P Allison
Jan 1, 1996·Annual Review of Immunology·D J LenschowJ A Bluestone
Mar 13, 2001·Annual Review of Immunology·B Salomon, J A Bluestone
Jan 16, 2007·Annual Review of Medicine·Philip L De Jager, David A Hafler
May 6, 1999·American Journal of Respiratory and Critical Care Medicine·A HaczkuE W Gelfand
Mar 10, 2001·The Journal of Clinical Investigation·T ChitnisS J Khoury
Jun 1, 1995·The Journal of Clinical Investigation·P S Linsley
Jun 1, 1997·The Journal of Clinical Investigation·K GençA T Reder
Apr 3, 2002·The Journal of Clinical Investigation·Vissia VigliettaDavid A Hafler
May 4, 1999·The Journal of Clinical Investigation·J R AbramsS Kang
Mar 11, 2000·The Journal of Clinical Investigation·J ReynoldsC D Pusey
Dec 1, 2012·International Journal of Biological Sciences·Yan-Ling WuHiroshi Sugiyama
Jun 15, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laura EspositoLinda S Wicker
Sep 22, 2012·Clinical & Developmental Immunology·Norihiko Watanabe, Hiroshi Nakajima
Mar 19, 2014·Immunology and Cell Biology·Delgertsetseg ChuluundorjAnne Camille La Flamme
May 5, 1999·Journal of Neuroimmunology·A WindhagenF Heidenreich

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.