IMMUNE SURVEILLANCE IN THE INJURED NERVOUS-SYSTEM - T-LYMPHOCYTES INVADE THE AXOTOMIZED MOUSE FACIAL MOTOR NUCLEUS AND AGGREGATE AROUND SITES OF NEURONAL DEGENERATION

Although the CNS is an established immune-privileged site, it is under surveillance by the immune system, particularly under pathological co nditions. In the current study we examined the lymphocyte infiltration , a key component of this neuroimmune surveillance, into the axotomize d facial motor nucleus and analyzed the changes in proinflammatory cyt okines and the blood-brain barrier. Peripheral nerve transection led t o a rapid influx of CD3-, CD11a (alpha L, LFA1 alpha)- and CD44-immuno reactive T-cells into the axotomized mouse facial motor nucleus, with a first, low-level plateau 2-4 d after injury, and a second, much stro nger increase at 14 d. These T-cells frequently formed aggregates and exhibited typical cleaved lymphocyte nuclei at the EM level. Immunohis tochemical colocalization with thrombospondin (TSP), a marker for phag ocytotic microglia, revealed aggregation of the T-cells around microgl ia removing neuronal debris. The massive influx of lymphocytes at day 14 was also accompanied by the synthesis of mRNA encoding IL1 beta, TN F alpha, and IFN-gamma. There was no infiltration by the neutrophil gr anulocytes, and the intravenous injection of horseradish peroxidase al so showed an intact blood-brain barrier. However, mice with severe com bined immunodeficiency (SCID), which lack differentiated T- and B-cell s, 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-ce lls into the mouse CNS during the retrograde reaction to axotomy. The striking aggregation of these lymphocytes around neuronal debris and p hagocytotic microglia suggests an important role for the immune survei llance during neuronal cell death in the injured nervous system.