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The Journal of Neuroscience, August 1, 1998, 18(15):5804-5816
Immune Surveillance in the Injured Nervous System:
T-Lymphocytes Invade the Axotomized Mouse Facial Motor Nucleus and
Aggregate around Sites of Neuronal Degeneration
Gennadij
Raivich1,
Leonard L.
Jones1,
Christian U. A.
Kloss1,
Alexander
Werner1,
Harald
Neumann2, and
Georg
W.
Kreutzberg1
Departments of 1 Neuromorphology and
2 Neuroimmunology, Max-Planck-Institute for
Neurobiology, D-82152 Martinsried, Germany
Although the CNS is an established immune-privileged site, it is
under surveillance by the immune system, particularly under pathological conditions. In the current study we examined the lymphocyte infiltration, a key component of this neuroimmune
surveillance, into the axotomized facial motor nucleus and analyzed the
changes in proinflammatory cytokines and the blood-brain barrier.
Peripheral nerve transection led to a rapid influx of CD3-, CD11a
( L, LFA1)- and CD44-immunoreactive T-cells into the axotomized mouse facial motor nucleus, with a first, low-level plateau 2-4 d
after injury, and a second, much stronger increase at 14 d. These
T-cells frequently formed aggregates and exhibited typical cleaved
lymphocyte nuclei at the EM level. Immunohistochemical colocalization
with thrombospondin (TSP), a marker for phagocytotic microglia,
revealed aggregation of the T-cells around microglia removing neuronal
debris. The massive influx of lymphocytes at day 14 was also
accompanied by the synthesis of mRNA encoding IL1 , TNF, and
IFN- . There was no infiltration by the neutrophil granulocytes, and
the intravenous injection of horseradish peroxidase also showed an
intact blood-brain barrier. However, mice with severe combined
immunodeficiency (SCID), which lack differentiated T- and
B-cells, still exhibited infiltration with CD11a-positive cells. These
CD11a-positive cells also aggregated around phagocytotic microglial
nodules.
In summary, there is a site-selective infiltration of activated T-cells
into the mouse CNS during the retrograde reaction to axotomy. The
striking aggregation of these lymphocytes around neuronal debris and
phagocytotic microglia suggests an important role for the immune
surveillance during neuronal cell death in the injured nervous
system.
Key words:
CD3; chemotaxis; microglia; cytokines; NK cells; scid
Copyright © 1998 Society for Neuroscience 0270-6474/98/18155804-13$05.00/0
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