T Cells Cause Trouble

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Science  29 Oct 2010:
Vol. 330, Issue 6004, pp. 561-563
DOI: 10.1126/science.330.6004.561-d

Multiple sclerosis (MS) results from inappropriate immune responses against antigens in the central nervous system (CNS). CD4+ T cells that make interleukin-17 (TH17 cells) are a major contributor to the development and pathogenesis of MS. Two recent studies now reveal how TH17 cells are regulated in the CNS and they how might contribute to disease. Using a mouse model of MS, Hao et al. show that natural killer (NK) cells residing in the CNS play a critical role in suppressing TH17 cell responses. NK cells do not act directly on the TH17 cells, however. Instead, they kill microglia, which present antigens and provide cytokine cues to direct TH17 cell differentiation in the CNS.

Siffrin et al. focus on how TH17 cells contribute to disease pathogenesis, also in a mouse model of MS. They show, through use of cell transfer experiments and intravital imaging, that TH17 cells (but not other CD4+ helper cell sub-sets) form long-lived contacts with neurons in the CNS of diseased mice. Neurons interacting with TH17 cells exhibited elevated amounts of intracellular calcium, which is indicative of neuronal toxicity, and in vitro, TH17 cells induced neuronal cell death. Together, these studies underscore the importance of TH17 cells in MS pathology and suggest that these cells, and NK cells, may be potential targets for therapeutic intervention.

J. Exp. Med. 209, 1907 (2010); Immunity 33, 424 (2010).

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