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

Clement, Mathew, Pearson, James, Gras, Stephanie, Van den berg, Hugo, Lissina, Anya, Llewellyn-Lacey, Sian, Willis, Mark, Dockree, Tamsin, McLaren, James, Ekeruche-Makinde, Julia, Gostick, Emma, Robertson, Neil, Burrows, Scott, Price, David, Wong, Florence, Peakman, Mark, Skowera, Ania and Wooldridge, Linda 2016. Targeted suppression of autoreactive CD8+ T-cell activation using blocking anti-CD8 antibodies. Scientific Reports 6 , 35332. 10.1038/srep35332

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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 speci city 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-speci c CD8+ T-cells are relatively CD8-independent. These generic di erences relate to an intrinsic dichotomy that segregates self-derived and exogenous antigen-speci c TCRs according to the monomeric interaction a nity 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 ndings 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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > R Medicine (General)
Publisher: Nature Publishing Group
ISSN: 2045-2322
Funders: Wellcome Trust
Related URLs:
Date of First Compliant Deposit: 17 October 2016
Date of Acceptance: 9 September 2016
Last Modified: 31 May 2018 13:33
URI: http://orca.cf.ac.uk/id/eprint/95381

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