Thursday, 27 December 2012

Tc17 a new player in cause of MS

IL-17-producing CD8+ T (Tc17) cells are detectable in MS lesions; however, their contribution to the disease is unknown. To identify functions of Tc17 cells, we induced EAE, a mouse model of MS, in mice lacking IFN regulatory factor 4 (IRF4). IRF4-deficient mice failed to generate Tc17 and Th17 cells and were resistant to EAE. After adoptive transfer of WT CD8+ T cells and subsequent immunization for EAE induction in these mice, the CD8+ T cells developed a Tc17 phenotype in the periphery but could not infiltrate the CNS. Similarly, transfer of small numbers of WT CD4+ T cells alone did not evoke EAE, but when transferred together with CD8+ T cells, IL-17-producing CD4+ (Th17) T cells accumulated in the CNS and mice developed severe disease. Th17 accumulation and development of EAE required IL-17A production by CD8+ T cells, suggesting that Tc17 cells are required to promote CD4+ T cell-mediated induction of EAE. Accordingly, patients with early-stage MS harbored a greater number of Tc17 cells in the cerebrospinal fluid than in peripheral blood. Our results reveal that Tc17 cells contribute to the initiation of CNS autoimmunity in mice and humans by supporting Th17 cell pathogenicity.



Many immunologists believed that CD4- T helper cells were the problem in MS, but the pathologists suggested that the dominant T in MS lesions were CD8 cells. So the EAE studies began to concentrate on CD8 T cells. When you see CD8 T cells you should first think virus! Now immunologists are reporting that a subset of CD8+ T cells called Tc17 cells.  They do not appear to have the destruction machinery of viral-killing CD8+ T cells, but it seems they can augment the damage caused by Th17 cells. Inhibition of these cells using blockade of Interleukin-17 or granulocyte macrophage colony stimulating factor is ongoing. Maybe another treatment for RRMS in the future.

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