Astrocytes protect the CNS: antigen-specific T helper cell responses are inhibited by astrocyte-induced upregulation of CTLA-4 (CD152).
Astrocytes are the first cells that are encountered by T cells invading the central nervous system (CNS) by crossing the blood-brain barrier. We show that primary astrocytes contribute to the immune privilege of the CNS by suppressing Th1 and Th2 cell activation, proliferation and effector function. Moreover, this astrocyte-mediated inhibition of Th effector cells was effective on already activated, proliferating cells. Transforming growth factor (TGF)-beta secreted by astrocytes or T cells was not the major factor in the inhibition. The inhibition of T-cell proliferation induced by astrocytes was mainly mediated by upregulation of CTLA-4 on already activated T cells, which occurred both with and without cell-cell contact. Upregulation of the inhibitory molecule CTLA-4 on autoreactive Th cells, as mediated by astrocytes, thus represents a novel mechanism for securing the immune privilege of the CNS.
Gimsa
Ulrike
U
Department of Neurology, University of Rostock, Gehlsheimer Strasse 20, 18147 Rostock, Germany. ulrike.gimsa@med.uni-rostock.de
ØRen
Anita
A
Pandiyan
Pushpa
P
Teichmann
Daniela
D
Bechmann
Ingo
I
Nitsch
Robert
R
Brunner-Weinzierl
Monika C
MC
D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D001253:Astrocytes / Q000276:immunology / Q000502:physiology*; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D015854:Up-Regulation
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D016212:Transforming Growth Factor beta