J Neuroimmunol. 2003 Jul;140(1-2):177-87
Wiendl H, Neuhaus O, Mehling M, Wintterle S, Schreiner B, Mitsdoerffer M, Wienhold W, Weissert R, Wessels J, Hartung HP, Weller M, Tolosa E, Melms A.
Department of Neurology, University of Tubingen, Hoppe-Seyler-Strasse 3, D-72076, Tubingen, Germany
Costimulatory signals play a key role in regulating T cell activation and are believed to have decisive influence in the inciting and perpetuating cellular effector mechanisms in autoimmune diseases such as multiple sclerosis (MS).
Inducible costimulator protein (ICOS), a recently identified member of the CD28-family, presumably affects the differentiation of Th1/Th2 cells after primary activation and modulates the immune response of effector/memory T cells.
This study examines the expression and functional role of ICOS costimulation in healthy donors and patients with MS.
After nonspecific or antigen-specific stimulation, ICOS is preferentially expressed on CD4 Th2-T cells.
ICOS-costimulation affects the production of Th1 and Th2 cytokines both in the absence and presence of B7/CD28 costimulation, thus suggesting that ICOS costimulation can modulate cytokine secretion also in a CD28-independent manner.
Levels of constitutive and inducible ICOS expression on human T cell subsets from peripheral blood were quantified in healthy donors and patients with MS.
Constitutive expression of ICOS on T cells varies between 0.1% and 42.3%.
There were no significant differences between both groups in the baseline expression or inducibility of ICOS on CD4 or CD8 T cells.
ICOS expression could be demonstrated on CSF T lymphocytes in patients with acute MS relapses but was not elevated compared with peripheral blood.
In essence we show that ICOS is upregulated on human T cells after stimulation and can modulate both Th1 and Th2 cytokine production in the absence and presence of B7-costimulation.
In MS patients we demonstrate the functionality of the ICOS costimulatory pathway.
Potential implications of ICOSL/ICOS interactions for MS immunopathogenesis are discussed.