The role of T cells in Neuroinflammation

I found Neuroprotective activities of CD4+CD25+ regulatory T cells in an animal model of Parkinson's disease to be a breath of fresh air since it provided an example of a good immune response after reading so many articles about immune responses gone awry. This article provided a wealth of information on the roles of regulatory and effector T cells. What I found particularly interesting in this article is the fact that regulatory T cells (Tregs) provided an overwhelming neuroprotective role in the substantia nigra pars compacta as Reynolds et al reported 90% protection of the dopaminergic neurons in the nigrostriatal system. In contrast, when MPTP injected mice were treated with effector T cells (Teffs), there was little evidence (2-18%) of neuroprotection (1087). It seems as though part of the reason Tregs are so effective as neuroprotectors is that they appear to recruit other anti-inflammatory agents. The study reported "significantly higher levels of IL-10 and TGF-β in MPTP/Treg-injected mice...compared with any other MPTP-intoxicated group" (1086).

Reynolds, et al did a very thorough job of looking at the role of Tregs and Teffs in several cellular aspects of Parkinson’s disease. They found that Tregs attenuated evidence of neurodegeneration in the Parkinson’s model mice by suppressing microglial activation. Microglial activation is thought to mediate neurodegeneration by nitrated-α synuclein as dopaminergic neurons are degenerated. This is believed to lead to the inflammatory cytotoxic cascade and it seems as though the Tregs are able to interrupt this cascade and protect nearly all the remaining dopaminergic receptors. While reading this, I was curious if any research was going on to effect the differentiation of T cells into Tregs as a possible therapy for Parkinson’s. I found one article that shows a possible therapy in The Journal of Immunology by Magdalena Polanczyk, et al: Cutting Edge: Estrogen drives expansion of the CD4+CD25+ Regulatory T cell compartment. This study showed that by treating mice with 17- β-estradiol, their cells expressed more FoxP3 (both in vivo and in vitro), which in turn caused an increased expression of Tregs and FoxP3. The increased expression of FoxP3 is especially interesting in that it controls the development and function of Tregs which would help explain their increased expression as well.

In further researching the role of T cells in neurology, I found that T cells help maintain cognitive functioning in the brain. In mice that were deficient in T cells, their learning and memory was impaired. However, when these mice were treated with transferred T cells from wild-type mice, their learning and memory deficits improved. Furthermore, Lewitus, et al showed that in vitro neural tissue treated with Teffs inhibited long term potentiation in the hippocampus which could prove to be an effective therapy for patients with MS and Alzheimer’s.

1. “FoxP3.” http://en.wikipedia.org/wiki/FOXP3
2.Lewitus G., et al. CD4+CD25- effector T cells inhibit hippocampal long term potentiation in vitro. European Journal of Neuroscience. 26: 1399-1406 (2007).
3. Polanczyk M., et al. Cutting Edge: Estrogen drives expansion of the CD4+CD25+ regulatory T cell compartment. The Journal of Immunology. 173: 2227-2230 (2004).
4. Reynolds, A. et al. Neuroprotective activities of CD4+CD25+ regulatory T cells in an animal model of Parkinson’s disease. Journal of Leukocyte Biology. 82: 1083-1094 (2007).