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A novel mechanism linking memory stem cells with innate immunity in protection against HIV-1 infection

O'Connell, Robert J.; Wang, Yufei; Whittall, Trevor; Neil, Stuart; Britton, Gary; Mistry, Mukesh; Rerks-Ngarm, Supachai; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Yu, Xuesong; Sato, Alicia; Michael, Nelson L.; Robb, Merlin L.; Kim, Jerome H.; Lehner, Thomas

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Authors

Robert J. O'Connell

Yufei Wang

Trevor Whittall Trevor.Whittall@uwe.ac.uk
Senior Lecturer in Biomedical Science (Immunology)

Stuart Neil

Gary Britton

Mukesh Mistry

Supachai Rerks-Ngarm

Punnee Pitisuttithum

Jaranit Kaewkungwal

Sorachai Nitayaphan

Xuesong Yu

Alicia Sato

Nelson L. Michael

Merlin L. Robb

Jerome H. Kim

Thomas Lehner



Abstract

© 2017 The Author(s). HIV infection affects 37 million people and about 1.7 million are infected annually. Among the phase III clinical trials only the RV144 vaccine trial elicited significant protection against HIV-1 acquisition, but the efficacy and immune memory were inadequate. To boost these vaccine functions we studied T stem cell memory (TSCM) and innate immunity. TSCM cells were identified by phenotypic markers of CD4+ T cells and they were further characterised into 4 subsets. These expressed the common IL-2/IL-15 receptors and another subset of APOBEC3G anti-viral restriction factors, both of which were upregulated. In contrast, CD4+ TSCM cells expressing CCR5 co-receptors and α4β7 mucosal homing integrins were decreased. A parallel increase in CD4+ T cells was recorded with IL-15 receptors, APOBEC3G and CC chemokines, the latter downmodulating CCR5 molecules. We suggest a novel mechanism of dual memory stem cells; the established sequential memory pathway, TSCM →Central →Effector memory CD4+ T cells and the innate pathway consisting of the 4 subsets of TSCM. Both pathways are likely to be activated by endogenous HSP70. The TSCM memory stem cell and innate immunity pathways have to be optimised to boost the efficacy and immune memory of protection against HIV-1 in the clinical trial.

Citation

O'Connell, R. J., Wang, Y., Whittall, T., Neil, S., Britton, G., Mistry, M., …Lehner, T. (2017). A novel mechanism linking memory stem cells with innate immunity in protection against HIV-1 infection. Scientific Reports, 7(1), https://doi.org/10.1038/s41598-017-01188-3

Journal Article Type Article
Acceptance Date Feb 2, 2017
Publication Date Dec 1, 2017
Deposit Date Apr 24, 2017
Publicly Available Date Apr 24, 2017
Journal Scientific Reports
Electronic ISSN 2045-2322
Publisher Nature Research (part of Springer Nature)
Peer Reviewed Peer Reviewed
Volume 7
Issue 1
DOI https://doi.org/10.1038/s41598-017-01188-3
Keywords stem cell memory, innate immunity, HIV-1
Public URL https://uwe-repository.worktribe.com/output/888963
Publisher URL http://dx.doi.org/10.1038/s41598-017-01188-3
Additional Information Corporate Creators : Mucosal Immunology Unit, Dept. of Virology; Kings College London, Henry Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD

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