Abstract

Determining the precise lifespan of human T cells is challenging due to an inability to distinguish between dividing and dying cells. We were able to utilize and naturally occurring mutant of HIV-1 to follow the fate of a single cell over a 20-year period. This study demonstrated that effector memory T cells can live for more than 17-years as opposed to the several months currently noted in the literature. CD4+ (helper) T cell depletion is a hallmark of HIV infection. While in part explained by direct infection of the cells by HIV, it is likely that other mechanisms exist. By combining studies of human peripheral blood with murine models we were able to demonstrate that CD4 lymphopenia in the presence of persistent elevations in levels of type 1 interferon can lead to sustained and progressive CD4+ T cell lymphopenia. IL-27 is an immunomodulatory cytokine with potent anti-HIV properties in vitro. In a study design to assess the potential effects of this cytokine on HIV replication in vivo, plasma IL-27 levels were measured in 462 patients with HIV infection and 43 controls. No associations were seen between plasma levels of IL-27 and plasma levels of HIV-1.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAI000585-25
Application #
8946286
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
25
Fiscal Year
2014
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Revell, Andrew D; Wang, Dechao; Perez-Elias, Maria-Jesus et al. (2018) 2018 update to the HIV-TRePS system: the development of new computational models to predict HIV treatment outcomes, with or without a genotype, with enhanced usability for low-income settings. J Antimicrob Chemother 73:2186-2196
Di Mascio, Michele; Srinivasula, Sharat; Kim, Insook et al. (2018) Total body CD4+ T cell dynamics in treated and untreated SIV infection revealed by in vivo imaging. JCI Insight 3:
Schreiber-Stainthorp, William; Sinharay, Sanhita; Srinivasula, Sharat et al. (2018) Brain 18F-FDG PET of SIV-infected macaques after treatment interruption or initiation. J Neuroinflammation 15:207
Baker, Jason V; Sharma, Shweta; Grund, Birgit et al. (2017) Systemic Inflammation, Coagulation, and Clinical Risk in the START Trial. Open Forum Infect Dis 4:ofx262
Barski, Artem; Cuddapah, Suresh; Kartashov, Andrey V et al. (2017) Rapid Recall Ability of Memory T cells is Encoded in their Epigenome. Sci Rep 7:39785
Sui, Hongyan; Zhou, Ming; Imamichi, Hiromi et al. (2017) STING is an essential mediator of the Ku70-mediated production of IFN-?1 in response to exogenous DNA. Sci Signal 10:
Srinivasula, Sharat; Gabriel, Erin; Kim, Insook et al. (2017) CD4+ levels control the odds of induction of humoral immune responses to tracer doses of therapeutic antibodies. PLoS One 12:e0187912
Sowrirajan, Bharatwaj; Saito, Yoshiro; Poudyal, Deepak et al. (2017) Interleukin-27 Enhances the Potential of Reactive Oxygen Species Generation from Monocyte-derived Macrophages and Dendritic cells by Induction of p47phox. Sci Rep 7:43441
Brooks, Kristina M; Garrett, Katy L; Kuriakose, Safia S et al. (2017) Decreased Absorption of Dolutegravir and Tenofovir Disoproxil Fumarate, But Not Emtricitabine, in an HIV-Infected Patient Following Oral and Jejunostomy-Tube Administration. Pharmacotherapy 37:e82-e89
Le Saout, Cecile; Luckey, Megan A; Villarino, Alejandro V et al. (2017) IL-7-dependent STAT1 activation limits homeostatic CD4+ T cell expansion. JCI Insight 2:

Showing the most recent 10 out of 65 publications