Astrocyte-induced T cell elimination is CD95 ligand dependent.
The brain has an intrinsic capacity to remove infiltrating T cells by inducing apoptosis. However, the pathways and cellular components driving this process are still under debate. Astrocytes seem to play an important role because they colocalize with apoptotic lymphocytes in vivo and induce apoptosis of transformed T cells in vitro. Since we previously demonstrated the expression of the death ligand CD95L (APO-1L/FasL) on astrocytes in the brain, we wanted to know whether nontransformed astrocytes induce cell death in nontransformed T cells, reflecting the in vivo situation and, if so, whether CD95/CD95 ligand interaction is important. T cell apoptosis measured by Annexin V binding and DNA fragmentation was significantly lower using CD95 ligand-deficient (gld) astrocytes compared to nondeficient controls. Moreover, neutralizing anti-CD95 ligand antibody reduced astrocyte-induced T cell apoptosis. Thus, adult astrocytes are capable of inducing the apoptotic death of T cells by involving the CD95/CD95 ligand pathway without undergoing cell death in vitro. Since astrocytic end-feet contribute to the formation of the blood-brain barrier, this depletion mechanism may play an important role as the first line of defense in the brain.
Bechmann
Ingo
I
Institute of Anatomy, Department of Cell and Neurobiology, Humboldt University Hospital Charité, 10098 Berlin, Germany.
Steiner
Barbara
B
Gimsa
Ulrike
U
Mor
Gil
G
Wolf
Susanne
S
Beyer
Martin
M
Nitsch
Robert
R
Zipp
Frauke
F
D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000502:physiology*; D001921:Brain / Q000276:immunology; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor