Intravenous gammaglobulin inhibits encephalitogenic potential of pathogenic T cells and interferes with their trafficking to the central nervous system, implicating sphingosine-1 phosphate receptor 1-mammalian target of rapamycin axis.
J Immunol
; 190(9): 4535-41, 2013 May 01.
Article
em En
| MEDLINE
| ID: mdl-23526819
ABSTRACT
Despite an increasing use of high-dose therapy of i.v. gammaglobulin (IVIg) in the treatment of various T cell- and Ab-mediated inflammatory and autoimmune diseases, comprehension of the mechanisms underlying its therapeutic benefit has remained a major challenge. Particularly, the effect of IVIg in T cell-mediated autoimmune conditions remains unexplored. Using an actively induced experimental autoimmune encephalomyelitis model, a T cell-mediated autoimmune condition, we demonstrate that IVIg inhibits the differentiation of naive CD4 T cells into encephalitogenic subsets (Th1 and Th17 cells) and concomitantly induces an expansion of Foxp3(+) regulatory T cells. Further, IVIg renders effector T cells less pathogenic by decreasing the expression of encephalitogenic molecular players like GM-CSF and podoplanin. Intriguingly and contrary to the current arguments, the inhibitory FcγRIIB is dispensable for IVIg-mediated reciprocal modulation of effector and regulatory CD4 subsets. Additionally, F(ab')2 fragments also retained this function of IVIg. IVIg or F(ab')2 fragments decrease the sphingosine-1 phosphate receptor on CD4 cells, thus sequestering these cells in the draining lymph nodes and decreasing their infiltration into the CNS. Our study reveals a novel role of Igs in the modulation of polarization and trafficking of T lymphocytes, accounting for the observed beneficial effect in IVIg therapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Imunoglobulinas Intravenosas
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Receptores de Lisoesfingolipídeo
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Encefalite
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Encefalomielite Autoimune Experimental
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Serina-Treonina Quinases TOR
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
França