ICOS is essential for the development of experimental autoimmune myasthenia gravis

SCOTT B., YANG H., Tuzun E., DONG C., FLAVELL R., CHRISTADOSS P.

JOURNAL OF NEUROIMMUNOLOGY, vol.153, pp.16-25, 2004 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 153
  • Publication Date: 2004
  • Doi Number: 10.1016/j.jneuroim.2004.04.019
  • Journal Name: JOURNAL OF NEUROIMMUNOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.16-25
  • Keywords: experimental autoimmune myasthenia gravis, myasthenia gravis, ICOS, B7RP-1, costimulation, autoimmunity, COLLAGEN-INDUCED ARTHRITIS, INDUCIBLE COSTIMULATOR, MOLECULE ICOS, MOTOR ENDPLATE, T-CELLS, LIGAND, CD28, EXPRESSION, INDUCTION, RESPONSES
  • Istanbul University Affiliated: Yes

Abstract

Lymphocyte costimulation via the inducible costimulatory molecule (ICOS) is required for effective humoral immunity development. Following immunization with Torpedo acetylcholine receptor (AChR), ICOS gene knockout (KO) mice were highly resistant to clinical experimental autoimmune myasthenia gravis (EAMG) development, had less serum AChR-specific immunoglobulins (Igs), and exhibited a diminutive germinal center (GC) reaction in secondary lymphoid tissues. Lymphocyte proliferation and both Th1 and Th2 differentiation in response to AChR and the AChR dominant alpha146-162 peptide were inhibited by the ICOS gene deficiency. ICOS-mediated lymphocyte costimulation is thus vital to the induction of T cell-mediated humoral immunity to AChR and the development of clinical EAMG. (C) 2004 Elsevier B.V. All rights reserved.