Immune cells involvement in CNS repair

Experimental models of acute CNS injuries

More than a decade ago, the group started to investigate experimental paradigms addressing a basic question in neuroscience: why have the brain and spinal cord, crucial organs of the body, lost their capacity for spontaneous repair following injury? We discovered, against the common wisdom at that time, that immune cells are pivotal for CNS neuroprotection and repair, but their spontaneous recruitment to the CNS is insufficient (1, 2); both circulating monocyte-derived macrophages, and helper T cells recognizing brain antigens were identified to have crucial and beneficial roles. The protective T cells were found to have specificity for self-brain antigens, leading us to formulate the model of “Protective autoimmunity” (3). Over the years, our group found that this response involves a network of T cells including effector and memory T cells, and regulatory T cells, whose role changes over time, and is temporally and spatially regulated (4). We also showed that this T cell network, in the context of acute injuries, is involved in facilitating recruitment of anti-inflammatory monocyte-derived macrophages to the CNS, and that these cells support tissue repair (5).

References

  1. Moalem, G., Leibowitz-Amit, R., Yoles, E., Mor, F., Cohen, I.R., and Schwartz, M. 1999. Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat Med 5:49-55.
     
  2. Rapalino, O., Lazarov-Spiegler, O., Agranov, E., Velan, G.J., Yoles, E., Fraidakis, M., Solomon, A., Gepstein, R., Katz, A., Belkin, M., Hadani, M., and Schwartz, M. 1998. Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nat Med 4:814-821.
     
  3. Schwartz, M. 2001. Protective autoimmunity as a T-cell response to central nervous system trauma: prospects for therapeutic vaccines. Prog Neurobiol 65:489-496.
     
  4. Raposo, C., Graubardt, N., Cohen, M., Eitan, C., London, A., Berkutzki, T., and Schwartz, M. 2014. CNS repair requires both effector and regulatory T cells with distinct temporal and spatial profiles. J Neurosci 34:10141-10155.
     
  5. Shechter, R., London, A., Varol, C., Raposo, C., Cusimano, M., Yovel, G., Rolls, A., Mack, M., Pluchino, S., Martino, G., Jung, S., and Schwartz, M. 2009. Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Med 6:e1000113.