Targeted suppression of autoreactive CD8+ T-cell activation using blocking anti-CD8 antibodies

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Abstract

CD8 + T-cells play a role in the pathogenesis of autoimmune diseases such as multiple sclerosis and type 1 diabetes. However, drugs that target the entire CD8 + T-cell population are not desirable because the associated lack of specificity can lead to unwanted consequences, most notably an enhanced susceptibility to infection. Here, we show that autoreactive CD8 + T-cells are highly dependent on CD8 for ligand-induced activation via the T-cell receptor (TCR). In contrast, pathogen-specific CD8 + T-cells are relatively CD8-independent. These generic differences relate to an intrinsic dichotomy that segregates self-derived and exogenous antigen-specific TCRs according to the monomeric interaction affinity with cognate peptide-major histocompatibility complex class I (pMHCI). As a consequence, "blocking" anti-CD8 antibodies can suppress autoreactive CD8 + T-cell activation in a relatively selective manner. These findings provide a rational basis for the development and in vivo assessment of novel therapeutic strategies that preferentially target disease-relevant autoimmune responses within the CD8 + T-cell compartment.

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APA

Clement, M., Pearson, J. A., Gras, S., Van Den Berg, H. A., Lissina, A., Llewellyn-Lacey, S., … Wooldridge, L. (2016). Targeted suppression of autoreactive CD8+ T-cell activation using blocking anti-CD8 antibodies. Scientific Reports, 6. https://doi.org/10.1038/srep35332

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