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CD20+ B cell depletion alters T cell homing.
Kap, Yolanda S; van Driel, Nikki; Laman, Jon D; Tak, Paul P; 't Hart, Bert A.
Afiliación
  • Kap YS; Department of Immunobiology, Biomedical Primate Research Centre, 2280 GH Rijswijk, The Netherlands;
J Immunol ; 192(9): 4242-53, 2014 May 01.
Article en En | MEDLINE | ID: mdl-24696233
Depleting mAbs against the pan B cell marker CD20 are remarkably effective in the treatment of autoimmune-mediated inflammatory disorders, but the underlying mechanisms are poorly defined. The primary objective of this study was to find a mechanistic explanation for the remarkable clinical effect of the anti-CD20 mAbs in a representative nonhuman primate autoimmune-mediated inflammatory disorder model, experimental autoimmune encephalomyelitis (EAE) in common marmosets, allowing detailed analysis of secondary lymphoid organs (SLO). We observed that the depletion of CD20(+) B cells creates a less immunostimulatory environment in the SLO reflected by reduced expression of MHC class II, CD40, CD83, and CD80/CD86. APCs isolated from SLO of B cell-depleted EAE monkeys were also less responsive to mitogenic stimulation. The depleted B cell areas were replenished by T cells, of which the majority expressed CD127 (IL-7R) and CCR7. Such effects were not detected in EAE marmosets treated with mAb against BLyS or APRIL, where B cell depletion via withdrawal of essential survival cytokines was not associated with a marked clinical effect. We propose that at least part of the efficacy of anti-CD20 mAb therapy is attributable to the sustained CCR7 expression on T cells within SLO, limiting their release into the circulation.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos B / Linfocitos T / Encefalomielitis Autoinmune Experimental / Anticuerpos Monoclonales Límite: Animals Idioma: En Revista: J Immunol Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos B / Linfocitos T / Encefalomielitis Autoinmune Experimental / Anticuerpos Monoclonales Límite: Animals Idioma: En Revista: J Immunol Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos