Targeted suppression of autoreactive CD8(+) T-cell activation using blocking anti-CD8 antibodies
Web of Science
AuthorClement, M; Pearson, JA; Gras, S; van den Berg, HA; Lissina, A; Llewellyn-Lacey, S; Willis, MD; Dockree, T; McLaren, JE; Ekeruche-Makinde, J; ...
Source TitleScientific Reports
PublisherNATURE PUBLISHING GROUP
University of Melbourne Author/sRossjohn, Jamie
AffiliationMicrobiology and Immunology
Document TypeJournal Article
CitationsClement, M., Pearson, J. A., Gras, S., van den Berg, H. A., Lissina, A., Llewellyn-Lacey, S., Willis, M. D., Dockree, T., McLaren, J. E., Ekeruche-Makinde, J., Gostick, E., Robertson, N. P., Rossjohn, J., Burrows, S. R., Price, D. A., Wong, F. S., Peakman, M., Skowera, A. & Wooldridge, L. (2016). Targeted suppression of autoreactive CD8(+) T-cell activation using blocking anti-CD8 antibodies. SCIENTIFIC REPORTS, 6 (1), https://doi.org/10.1038/srep35332.
Access StatusOpen Access
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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