title: Expansion of CD4+CD25+ regulatory T cells by intravenous immunoglobulin: a critical factor in controlling experimental autoimmune encephalomyelitis.
abstract: The clinical use of intravenous immunoglobulin (IVIg) based on its immunomodulatory and anti-inflammatory potential remains an ongoing challenge. Fcgamma receptor-mediated effects of IVIg, although well elucidated in certain pathologies, cannot entirely account for its proven benefit in several autoimmune disorders mediated by autoreactive T cells. In this study, we show that prophylactic infusion of IVIg prevents the development of experimental autoimmune encephalomyelitis (EAE), an accepted animal model for multiple sclerosis (MS). The protection was associated with peripheral increase in CD4+CD25+Foxp3+ regulatory T cell (Treg) numbers and function. The protection was Treg-mediated because IVIg failed to protect against EAE in mice that were depleted of the Treg population. Rather than inducing de novo generation from conventional T cells, IVIg had a direct effect on proliferation of natural Treg. In conclusion, our results highlight a novel mechanism of action of IVIg and provide a rationale to test the use of IVIg as an immunomodulatory tool to enhance Treg in early onset MS and other autoimmune and inflammatory conditions.
authors.affiliation: Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, UMR S 872, Inserm U872, France.
authors.forename: Amal
authors.initials: A
authors.lastname: Ephrem
authors.forename: Souleima
authors.initials: S
authors.lastname: Chamat
authors.forename: Catherine
authors.initials: C
authors.lastname: Miquel
authors.forename: Sylvain
authors.initials: S
authors.lastname: Fisson
authors.forename: Luc
authors.initials: L
authors.lastname: Mouthon
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Caligiuri
authors.forename: Sandrine
authors.initials: S
authors.lastname: Delignat
authors.forename: Sriramulu
authors.initials: S
authors.lastname: Elluru
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Bayry
authors.forename: Sebastien
authors.initials: S
authors.lastname: Lacroix-Desmazes
authors.forename: José L
authors.initials: JL
authors.lastname: Cohen
authors.forename: Benoît L
authors.initials: BL
authors.lastname: Salomon
authors.forename: Michel D
authors.initials: MD
authors.lastname: Kazatchkine
authors.forename: Srini V
authors.initials: SV
authors.lastname: Kaveri
authors.forename: Namita
authors.initials: N
authors.lastname: Misra
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology* / Q000627:therapeutic use; D007155:Immunologic Factors / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors