The CD28 related molecule ICOS
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The CD28 related molecule ICOS : T cell modulation in the presence and absence of B7.1/2 and regulational expression in multiple sclerosis. / Wiendl, Heinz; Neuhaus, Oliver; Mehling, Matthias; Wintterle, Sabine; Schreiner, Bettina; Mitsdoerffer, Meike; Wienhold, Wolfgang; Weissert, Robert; Wessels, Johannes; Hartung, Hans-Peter; Weller, Michael; Tolosa, Eva; Melms, Arthur.
in: J NEUROIMMUNOL, Jahrgang 140, Nr. 1-2, 01.07.2003, S. 177-87.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The CD28 related molecule ICOS
T2 - T cell modulation in the presence and absence of B7.1/2 and regulational expression in multiple sclerosis
AU - Wiendl, Heinz
AU - Neuhaus, Oliver
AU - Mehling, Matthias
AU - Wintterle, Sabine
AU - Schreiner, Bettina
AU - Mitsdoerffer, Meike
AU - Wienhold, Wolfgang
AU - Weissert, Robert
AU - Wessels, Johannes
AU - Hartung, Hans-Peter
AU - Weller, Michael
AU - Tolosa, Eva
AU - Melms, Arthur
PY - 2003/7/1
Y1 - 2003/7/1
N2 - 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.
AB - 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.
KW - Adjuvants, Immunologic
KW - Adult
KW - Animals
KW - Antigens, CD
KW - Antigens, CD28
KW - Antigens, CD80
KW - Antigens, CD86
KW - Antigens, Differentiation, T-Lymphocyte
KW - Cell Line
KW - Coculture Techniques
KW - Female
KW - Flow Cytometry
KW - Humans
KW - Inducible T-Cell Co-Stimulator Protein
KW - Interferon-beta
KW - Interferon-gamma
KW - Interleukin-4
KW - L Cells (Cell Line)
KW - Male
KW - Membrane Glycoproteins
KW - Mice
KW - Middle Aged
KW - Multiple Sclerosis
KW - Peptides
KW - Receptors, Chemokine
KW - T-Lymphocyte Subsets
KW - Th1 Cells
KW - Th2 Cells
KW - Transfection
KW - Up-Regulation
M3 - SCORING: Journal article
C2 - 12864987
VL - 140
SP - 177
EP - 187
JO - J NEUROIMMUNOL
JF - J NEUROIMMUNOL
SN - 0165-5728
IS - 1-2
ER -