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Virology Research Journal
Volume 1 Issue 4 Vaccines World 2017
Page 20
November 09-10, 2017 Vienna, Austria
21st World Congress and Exhibition on
VACCINES, VACCINATION & IMMUNIZATION
A novel mechanism linking memory stem cells with
innate immunity in protection against HIV-1 infection
Thomas Lehner1, Yufei Wang 1, Trevor Whittall1, Stuart Neil2 and Mukesh
Mistry1
1Mucosal Immunology Unit, Kings College London, UK
2Kings College London, UK
HIV infection affects 37 million people and about 1.7
million are infected annually. Only the RV144 vaccine
phase III clinical trial elicited significant protection against
HIV-1 acquisition, but the efficacy and immune memory were
inadequate. To boost these two critical functions of the vaccine
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 characterized into 4 subsets. These
consisted of IL-2/IL-15 receptors and APOBEC3G anti-viral
restriction factors, which were upregulated, whereas CCR5
co-receptors and α4β7 mucosal homing integrins were
decreased. A parallel increase in CD4+ T cells was recorded of
the IL-15 receptors, APOBEC3G and CC chemokines, with a
decrease in CCR5 expression. 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 hallmark of cellular stress. The memory stem cells
and innate immunity pathways should be optimized to boost
the efficacy and immune memory of protection against HIV-
1. TSCM are likely to be activated by inducible HSP70, as PES
(phenylethynesulphonamide), a small molecular inhibitor
induced a dose-dependent inhibition of TSCM. The link
between memory stem cells and innate immunity suggests
a novel mechanism of inhibiting HIV-1 acquisition, by
decreasing CCR5 and α4β7, increasing IL-15/IL-2 receptors
and HIV-1 restriction factors.
Recent Publications
• Wang Y, Whittall T, Neil S, Britton G, Mistry M
(2017) A novel mechanism linking memory stem cells
with innate immunity in protection against HIV-1
infection. Scientific reports. 7(1):1057.
• Wang Y, Rahman D, Mistry M and Lehner T (2016) The
effect of cellular stress on T and B cell memory pathways
in immunized and unimmunized BALB/c mice. J. Biol.
Chem. 291(39):20707-20717.
• Wang Y, Lavender P, Watson J, Arno M and Lehner
(2015) Stress activated DC induce dual IL-15 and IL-b
mediated pathways, which may elicit CD4+ T cells and
IFN stimulated genes. J. Biol. Chem. 290(25):15595-609.
• Lewis DJM, Wang Y, Huo Z, Gimza R, Babaahmady K
et. al. (2014) Effect of vaginal immunization in women
with HIVgp140 and HSP70 on HIV-1 replication,
innate and T cell adaptive immunity in women. J. Virol.
88(20):11648-11657.
• Wang Y, Whittall T, Rahman D, Bunnik EM, Vaughan
R (2012) The role of innate apobec3g and adaptive aid
immune responses in HLA-HIV/SIV immunized SHIV
infected macaques. PlosOne. 7(4): e34433
Biography
Thomas Lehner is a Professor of Basic and Applied Immunology from London
University. He pursued MB, BS London, MD London, FDS RCS, FRC Path,
F Med Sci. He has several Prizes and honors to his credit which includes:
Besredka Prize of the Pasteur Institute, Lyon, France; Honorary Doctorate,
Karolinska Institute, Stockholm, Sweden; Honorary Life President of the
International Society for Behcet’s Disease; Appointed Commander of the British
Empire (CBE) and Honorary Fellow of the Royal Society of Medicine. He has
few selected international appointments including: Member of NIH (NIAID),
Bethesda US Review Committee Research Grants 1999-2007; Member of
Scientific Committee of the International Mucosal Immunology 1997-2006 and
Member of the Scientific Committee of the Institute of Virology of the University of
Maryland (1998-2002). He has 265 peer-reviewed papers published in scientific
journals. Over the past 20 years his research involved animals and humans,
preventing HIV and SIV infections, focus on mucosal immunization, generation
of CC-chemokines, CCR5 coreceptors stress agents and alloimmunization.
Thomas Lehner et al., Virol Res J 2017, 1:4