Tejera-Alhambra et al. Perforin Expression by CD4+ Regulatory T Cells Increases at Multiple Sclerosis Relapse: Sex Differences. Int J Mol Sci. 2012;13:6698-710.
Multiple sclerosis (MS) represents the leading cause of neurological deficit among young adults, affecting women more frequently than men. In MS, the extent of central nervous system lesions is determined by the net balance between self-reactive and regulatory T-cells at any given time, among other factors, as well as by the effect of inflammatory response. Here, we studied both CD4+ and CD8+ T(Reg) in parallel in blood and CSF during MS relapse. A recruitment of both regulatory CD4+ and CD8+ T cells (T(Reg)) within the cerebrospinal fluid (CSF) takes place during MS relapse. The presence of CD4+ T(Reg) in CSF was higher in women than in men, which could account for the sexual dimorphism in the incidence of MS. A direct correlation between plasma oestradiol E2 (oestrogen female sex hormone) and IL-2 (T cell growth factor) levels was observed, in line with a putative circuit of oestrogen and perforin (a pore forming molecule that punches holes in cells/bacteria and kills them) expression by CD4+ T(Reg) playing a role in MS. Also, serum interferon-alpha (anti-viral molecule) was higher in females, with direct correlation with serum E2 levels. This is the first study to analyze perforin expression by CD4+ T(Reg) in MS, which was greatly enhanced in CSF, what points out a relevant role of this molecule in the suppressive effects of the CD4+ T(Reg) in MS, and contributes to the understanding of MS pathophysiology.
We have talked about Treg or T regulatory cells before. These cells are thought to prevent autoimmunity from developing. In this study they report more T reg cells in the cerebrospinal fluid of women during relapse. The authors suggest that this is causally related but would more T reg surely not be related with more regulation and so less disease? This is just a chicken and egg study that is difficult to interpret.