Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2012 Sep 11;109(37):E2412-3; author reply E2414.
doi: 10.1073/pnas.1209124109. Epub 2012 Aug 3.

Effect of CC chemokine receptor 4 antagonism on the evolution of experimental autoimmune encephalomyelitis

Shivashankar Othy, Selma Topçu, Srini V Kaveri, Jagadeesh Bayry
Comment

Effect of CC chemokine receptor 4 antagonism on the evolution of experimental autoimmune encephalomyelitis

Shivashankar Othy et al. Proc Natl Acad Sci U S A. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

Conflict of interest statement: J.B. holds a patent on the use of a CCR4 antagonist as an adjuvant, specifically in an immunogenic composition comprising an antigen that elicits an immune response against a pathogen or tumour (WO2009150433, European and US patent).

Figures

Fig. 1.
Fig. 1.
Antagonizing CCR4 does not affect the course and severity of EAE. Ten-week-old female C57BL/6J mice (Janvier Laboratories) were immunized with 200 μg of myelin oligodendrocyte glycoprotein (MOG35–55; MEVGWYRSPFSRVVHLYRNGK) peptide in complete Freund’s adjuvant containing 500 μg of nonviable Mycobacterium tuberculosis (H37RA). Three hundred nanograms of pertussis toxin (List Biologic Laboratories) in PBS was injected i.v. on the day of immunization and 48 h later. All animal studies were performed according to the guidelines of the Charles Darwin Ethical Committee for Animal Experimentation (Université Pierre et Marie Curie) at the pathogen-free animal facility of the Centre de Recherche des Cordeliers. The CCR4 antagonist AF399/420/18025 was dissolved in DMSO and the final solution for injection was prepared in 10% DMSO to maintain the solubility of the antagonist. Mice in the CCR4 antagonist treatment group received 1.5 μg of antagonist in 100 μL volume injected i.p. daily either from d0 to d4 (prophylaxis regimen, ●) or after onset of clinical signs from d8 to d12 (therapeutic regimen, ▲). Control mice received 100 μL of 10% DMSO from d0 to d4 (○). Mice were assessed daily for the development of clinical signs according to the following scoring pattern: 0, no signs; 1, tail paresis; 2, hind limb paresis; 3, hind limb paralysis; 4, tetraplegia; and 5, moribund. Error bars represent SEM. (A) Daily mean clinical scores of each group (9–10 mice per group; P > 0.05, two-way ANOVA with Bonferroni post t test). ns, nonsignificant. (B) Mean maximal score of each group during the entire period of study (P > 0.05, Mann–Whitney U test). (C) Percentage incidence of EAE in each group plotted against time.
See this image and copyright information in PMC

Comment on

References

    1. Poppensieker K, et al. CC chemokine receptor 4 is required for experimental autoimmune encephalomyelitis by regulating GM-CSF and IL-23 production in dendritic cells. Proc Natl Acad Sci USA. 2012;109:3897–3902. - PMC - PubMed
    1. Bayry J, et al. In silico identified CCR4 antagonists target regulatory T cells and exert adjuvant activity in vaccination. Proc Natl Acad Sci USA. 2008;105:10221–10226. - PMC - PubMed
    1. Newhouse B, et al. Racemic and chiral lactams as potent, selective and functionally active CCR4 antagonists. Bioorg Med Chem Lett. 2004;14:5537–5542. - PubMed
    1. Pere H, et al. A CCR4 antagonist combined with vaccines induces antigen-specific CD8+ T cells and tumor immunity against self antigens. Blood. 2011;118:4853–4862. - PubMed
    1. Iellem A, et al. Unique chemotactic response profile and specific expression of chemokine receptors CCR4 and CCR8 by CD4(+)CD25(+) regulatory T cells. J Exp Med. 2001;194:847–853. - PMC - PubMed

MeSH terms

Substances

LinkOut - more resources