Inhibition by CTLA4Ig of experimental allergic encephalomyelitis - PubMed (original) (raw)
. 1996 Jun 15;156(12):4916-24.
Affiliations
- PMID: 8648142
Inhibition by CTLA4Ig of experimental allergic encephalomyelitis
T Arima et al. J Immunol. 1996.
Abstract
B7-1 and B7-2 are well characterized costimulatory ligands on Ag presentation cells for the CD28 and CTLA4 receptors on T cells. The fusion protein CTLA4Ig can block this interaction and prevent specific T cell activation. The development of fatal CD4+ T cell-mediated experimental allergic encephalomyelitis (EAE) in susceptible female Lewis rats was optimized by immunization with 20 mg of guinea pig spinal cord homogenate in CFA on day 0 with three doses of 1 microgram pertussis toxin given i.v. on days 0, 3, and 7. This immunization regimen uniformly resulted in the development of severe clinical neurologic signs of EAE with 100% mortality by day 17 postimmunization. Treatment with 0.5 mg/dose of rhCTLA4-Ig on days - 2, 0, 3, 6, 9, 12, 15 and 18 significantly decreased the incidence, delayed the onset, and reduced the severity of clinical EAE (p = 0.0002 vs control by the Mann-Whitney U test) enough to completely prevent fatal EAE, whereas treatment with control human IgG had no effect. Histologically, perivascular neutrophilic infiltrates were also dramatically decreased in the spinal cords of animals treated with CTLA4 but not in those treated with control human IgG. The proliferative response to encephalitogenic Ags (guinea pig myelin basic protein and proteolipid protein) by lymph node cells from animals immunized with guinea pig spinal cord 10 days before was also significantly suppressed in vitro by CTLA4Ig (1 microg/ml). However, the protective effect of CTLA4Ig could be completely prevented by the daily i.p. administration, from day 0 to 10, of exogenous human rIL-2 (180,000 IU). These results indicate a critical requirement of the costimulatory B7/CD28 pathway early in the development of CD4+ T cell-mediated EAE in the rat.
Similar articles
- Ex vivo treatment of antigen-presenting cells with CTLA4Ig and encephalitogenic peptide prevents experimental autoimmune encephalomyelitis in the Lewis rat.
Khoury SJ, Gallon L, Verburg RR, Chandraker A, Peach R, Linsley PS, Turka LA, Hancock WW, Sayegh MH. Khoury SJ, et al. J Immunol. 1996 Oct 15;157(8):3700-5. J Immunol. 1996. PMID: 8871673 - Role of B7:CD28/CTLA-4 in the induction of chronic relapsing experimental allergic encephalomyelitis.
Perrin PJ, Scott D, Quigley L, Albert PS, Feder O, Gray GS, Abe R, June CH, Racke MK. Perrin PJ, et al. J Immunol. 1995 Feb 1;154(3):1481-90. J Immunol. 1995. PMID: 7529805 - Effect of DAB(389)IL-2 immunotoxin on the course of experimental autoimmune encephalomyelitis in Lewis rats.
Phillips SM, Bhopale MK, Constantinescu CS, Ciric B, Hilliard B, Ventura E, Lavi E, Rostami A. Phillips SM, et al. J Neurol Sci. 2007 Dec 15;263(1-2):59-69. doi: 10.1016/j.jns.2007.05.032. Epub 2007 Jul 2. J Neurol Sci. 2007. PMID: 17603081 - Differential requirements of naïve and memory T cells for CD28 costimulation in autoimmune pathogenesis.
Perrin PJ, Lovett-Racke A, Phillips SM, Racke MK. Perrin PJ, et al. Histol Histopathol. 1999 Oct;14(4):1269-76. doi: 10.14670/HH-14.1269. Histol Histopathol. 1999. PMID: 10506942 Review.
Cited by
- Dendritic cells, T cells and their interaction in rheumatoid arthritis.
Wehr P, Purvis H, Law SC, Thomas R. Wehr P, et al. Clin Exp Immunol. 2019 Apr;196(1):12-27. doi: 10.1111/cei.13256. Epub 2019 Jan 21. Clin Exp Immunol. 2019. PMID: 30589082 Free PMC article. Review. - A comprehensive review on the role of co-signaling receptors and Treg homeostasis in autoimmunity and tumor immunity.
Kumar P, Bhattacharya P, Prabhakar BS. Kumar P, et al. J Autoimmun. 2018 Dec;95:77-99. doi: 10.1016/j.jaut.2018.08.007. Epub 2018 Aug 31. J Autoimmun. 2018. PMID: 30174217 Free PMC article. Review. - Vstm3 is a member of the CD28 family and an important modulator of T-cell function.
Levin SD, Taft DW, Brandt CS, Bucher C, Howard ED, Chadwick EM, Johnston J, Hammond A, Bontadelli K, Ardourel D, Hebb L, Wolf A, Bukowski TR, Rixon MW, Kuijper JL, Ostrander CD, West JW, Bilsborough J, Fox B, Gao Z, Xu W, Ramsdell F, Blazar BR, Lewis KE. Levin SD, et al. Eur J Immunol. 2011 Apr;41(4):902-15. doi: 10.1002/eji.201041136. Epub 2011 Mar 18. Eur J Immunol. 2011. PMID: 21416464 Free PMC article. - Abatacept does not induce direct gene expression changes in antigen-presenting cells.
Carman JA, Davis PM, Yang WP, Zhu J, Chang H, He A, Truong A, Suchard SJ, Nadler SG. Carman JA, et al. J Clin Immunol. 2009 Jul;29(4):479-89. doi: 10.1007/s10875-009-9282-z. Epub 2009 Mar 4. J Clin Immunol. 2009. PMID: 19259798 - Coronavirus-induced demyelination occurs in the absence of CD28 costimulatory signals.
Gonzales DM, Fu L, Li Y, Das Sarma J, Lavi E. Gonzales DM, et al. J Neuroimmunol. 2004 Jan;146(1-2):140-3. doi: 10.1016/j.jneuroim.2003.10.053. J Neuroimmunol. 2004. PMID: 14698856 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Other Literature Sources
Research Materials