Treatment with native heterodimeric IL-15 increases cytotoxic lymphocytes and reduces SHIV RNA in lymph nodes

PLoS Pathogens
Dionysios C WatsonGeorge N Pavlakis

Abstract

B cell follicles in secondary lymphoid tissues represent an immune privileged sanctuary for AIDS viruses, in part because cytotoxic CD8+ T cells are mostly excluded from entering the follicles that harbor infected T follicular helper (TFH) cells. We studied the effects of native heterodimeric IL-15 (hetIL-15) treatment on uninfected rhesus macaques and on macaques that had spontaneously controlled SHIV infection to low levels of chronic viremia. hetIL-15 increased effector CD8+ T lymphocytes with high granzyme B content in blood, mucosal sites and lymph nodes, including virus-specific MHC-peptide tetramer+ CD8+ cells in LN. Following hetIL-15 treatment, multiplexed quantitative image analysis (histo-cytometry) of LN revealed increased numbers of granzyme B+ T cells in B cell follicles and SHIV RNA was decreased in plasma and in LN. Based on these properties, hetIL-15 shows promise as a potential component in combination immunotherapy regimens to target AIDS virus sanctuaries and reduce long-term viral reservoirs in HIV-1 infected individuals. ClinicalTrials.gov NCT02452268.

References

Dec 11, 1999·Journal of Medical Primatology·R C TanC Cheng-Mayer
Nov 16, 2002·Immunity·Sigrid DuboisYutaka Tagaya
May 8, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marion BerardDavid F Tough
Nov 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michelle M SandauStephen C Jameson
Mar 23, 2006·Annual Review of Immunology·Averil MaPatrick Burkett
May 13, 2006·The Journal of Clinical Investigation·Louis J PickerFrancois Villinger
Jun 8, 2006·Proceedings of the National Academy of Sciences of the United States of America·Mark P RubinsteinJonathan Sprent
Oct 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Thomas A StoklasekLeo Lefrançois
Mar 7, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anna HryniewiczGenoveffa Franchini
May 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Elizabeth ConnickPamela J Skinner
Sep 24, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mark E DudleySteven A Rosenberg
Jan 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Matthew D EberlyJoseph J Mattapallil
Jul 17, 2009·Blood·Carolina BergerStanley R Riddell
Aug 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cristina BergamaschiGeorge N Pavlakis
Sep 30, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yvonne M MuellerPeter D Katsikis
Feb 14, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sara L ColpittsLeo Lefrançois
Aug 28, 2012·The Journal of Clinical Investigation·Constantinos PetrovasRichard A Koup
Dec 21, 2012·The Journal of Experimental Medicine·Matthieu PerreauGiuseppe Pantaleo
Jan 30, 2013·Proceedings of the National Academy of Sciences of the United States of America·Vainav PatelGeorge N Pavlakis
Jun 19, 2013·Immunological Reviews·Korey R DemersMichael R Betts
Aug 24, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sara L ColpittsLeo Lefrançois
Jan 23, 2014·Proceedings of the National Academy of Sciences of the United States of America·Guangwei CuiKoichi Ikuta
Sep 18, 2014·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Antonio ValentinGeorge N Pavlakis
Sep 19, 2014·World Journal of Gastrointestinal Oncology·Juana Gonzalo-MarinManuel Perez-Miranda

❮ Previous
Next ❯

Citations

Jun 12, 2018·Current Opinion in HIV and AIDS·Maria PinoVincent C Marconi
Dec 27, 2018·Current Opinion in HIV and AIDS·Yin XuElizabeth Connick
Dec 27, 2018·Current Opinion in HIV and AIDS·Timothy N Hoang, Mirko Paiardini
Oct 28, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Afam A OkoyeLouis J Picker
Mar 12, 2020·Expert Opinion on Biological Therapy·Karin M KnudsonSofia R Gameiro
Mar 14, 2020·Current Opinion in HIV and AIDS·Mala K Maini, Dimitra Peppa
Aug 5, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Satoru WatanabeKazuyasu Mori
Oct 28, 2019·Frontiers in Immunology·Sarah E BeckJoel N Blankson
Aug 27, 2019·Frontiers in Immunology·Federico Perdomo-CelisMaria T Rugeles
Jun 17, 2020·Journal of Immunology Research·Hager MohamedFred C Krebs
May 5, 2018·Frontiers in Immunology·Nicolas HuotMichaela Müller-Trutwin
Mar 7, 2021·Cancers·Cristina BergamaschiGeorge N Pavlakis
Mar 30, 2020·Cell·David M MargolisAngela Wahl
Apr 20, 2021·Frontiers in Immunology·Shawn Abeynaike, Silke Paust
Jul 7, 2021·PLoS Pathogens·Fredrik BarrenäsMichael Gale
Jul 29, 2021·PLoS Computational Biology·Jonathan W CodyElsje Pienaar

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
biopsies
PCR
flow filtration
Flow

Clinical Trials Mentioned

NCT02452268

Software Mentioned

Leica
SAS
Imaris
histo
Excel
FlowJo
Graph Pad
cytometry
Prism

Related Concepts

Related Feeds

B cell Activation

B cell activation is initiated by the ligation of the B cell receptor with antigen and ultimately results in the production of protective antibodies against potentially pathogenic invaders. Here is the latest research.