Expansion of CD4+CD25+ regulatory T cells by intravenous immunoglobulin: a critical factor in controlling experimental autoimmune encephalomyelitis.
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.
Ephrem
Amal
A
Centre de Recherche des Cordeliers, Université Pierre et Marie Curie-Paris 6, UMR S 872, Inserm U872, France.
Chamat
Souleima
S
Miquel
Catherine
C
Fisson
Sylvain
S
Mouthon
Luc
L
Caligiuri
Giuseppina
G
Delignat
Sandrine
S
Elluru
Sriramulu
S
Bayry
Jagadeesh
J
Lacroix-Desmazes
Sebastien
S
Cohen
José L
JL
Salomon
Benoît L
BL
Kazatchkine
Michel D
MD
Kaveri
Srini V
SV
Misra
Namita
N
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
D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors