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More MS news articles for November 2002

Astrocyte-induced T cell elimination is CD95 ligand dependent

http://www.elsevier.com/gej-ng/10/27/37/137/25/33/abstract.html

Journal of Neuroimmunology, Vol. 132 (1-2) (2002) pp. 60-65
Ingo Bechmann a, Barbara Steiner a, Ulrike Gimsa a, Gil Mor b, Susanne Wolf a, Martin Beyer c, Robert Nitsch a 1 and Frauke Zipp c
a Institute of Anatomy, Department of Cell and Neurobiology, Humboldt University Hospital Charité, 10098 Berlin, Germany
b Department of OB/GYN, Reproductive Immunology, Yale University, New Haven, CT, USA
c Neuroscience Research Center, Institute of Neuroimmunology, Humboldt University Hospital Charité, Campus Virchow, Augustenburger Platz 1, Forschungshaus 2, OG/R.535, 10098 Berlin, Germany

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.