IL-15 promotes activation and expansion of CD8+ T cells in HIV-1 infection

Souheil Antoine Younes, Michael L. Freeman, Joseph C. Mudd, Carey L. Shive, Arnold Reynaldi, Soumya Panigrahi, Jacob Estes, Claire Deleage, Carissa Lucero, Jodi Anderson, Timothy W. Schacker, Miles P. Davenport, Joseph M. McCune, Peter W. Hunt, Sulggi A. Lee, Sergio Serrano-Villar, Robert L. Debernardo, Jeffrey M. Jacobson, David H. Canaday, Raafick Pierre SekalyBenigno Rodriguez, Scott F. Sieg, Michael M. Lederman

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

In HIV-1-infected patients, increased numbers of circulating CD8+ T cells are linked to increased risk of morbidity and mortality. Here, we identified a bystander mechanism that promotes CD8 T cell activation and expansion in untreated HIV-1-infected patients. Compared with healthy controls, untreated HIV-1-infected patients have an increased population of proliferating, granzyme B+, CD8+ T cells in circulation. Vβ expression and deep sequencing of CDR3 revealed that in untreated HIV-1 infection, cycling memory CD8 T cells possess a broad T cell repertoire that reflects the repertoire of the resting population. This suggests that cycling is driven by bystander activation, rather than specific antigen exposure. Treatment of peripheral blood mononuclear cells with IL-15 induced a cycling, granzyme B+ phenotype in CD8+ T cells. Moreover, elevated IL-15 expression in the lymph nodes of untreated HIV-1-infected patients correlated with circulating CD8+ T cell counts and was normalized in these patients following antiretroviral therapy. Together, these results suggest that IL-15 drives bystander activation of CD8+ T cells, which predicts disease progression in untreated HIV-1-infected patients and suggests that elevated IL-15 may also drive CD8+ T cell expansion that is linked to increased morbidity and mortality in treated patients.

Original languageEnglish (US)
Pages (from-to)2745-2756
Number of pages12
JournalJournal of Clinical Investigation
Volume126
Issue number7
DOIs
StatePublished - Jul 1 2016
Externally publishedYes

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Interleukin-15
HIV Infections
HIV-1
T-Lymphocytes
Granzymes
Morbidity
High-Throughput Nucleotide Sequencing
Mortality
Population
Disease Progression
Blood Cells
Cell Count
Lymph Nodes
Phenotype
Antigens

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Younes, S. A., Freeman, M. L., Mudd, J. C., Shive, C. L., Reynaldi, A., Panigrahi, S., ... Lederman, M. M. (2016). IL-15 promotes activation and expansion of CD8+ T cells in HIV-1 infection. Journal of Clinical Investigation, 126(7), 2745-2756. https://doi.org/10.1172/JCI85996

IL-15 promotes activation and expansion of CD8+ T cells in HIV-1 infection. / Younes, Souheil Antoine; Freeman, Michael L.; Mudd, Joseph C.; Shive, Carey L.; Reynaldi, Arnold; Panigrahi, Soumya; Estes, Jacob; Deleage, Claire; Lucero, Carissa; Anderson, Jodi; Schacker, Timothy W.; Davenport, Miles P.; McCune, Joseph M.; Hunt, Peter W.; Lee, Sulggi A.; Serrano-Villar, Sergio; Debernardo, Robert L.; Jacobson, Jeffrey M.; Canaday, David H.; Sekaly, Raafick Pierre; Rodriguez, Benigno; Sieg, Scott F.; Lederman, Michael M.

In: Journal of Clinical Investigation, Vol. 126, No. 7, 01.07.2016, p. 2745-2756.

Research output: Contribution to journalArticle

Younes, SA, Freeman, ML, Mudd, JC, Shive, CL, Reynaldi, A, Panigrahi, S, Estes, J, Deleage, C, Lucero, C, Anderson, J, Schacker, TW, Davenport, MP, McCune, JM, Hunt, PW, Lee, SA, Serrano-Villar, S, Debernardo, RL, Jacobson, JM, Canaday, DH, Sekaly, RP, Rodriguez, B, Sieg, SF & Lederman, MM 2016, 'IL-15 promotes activation and expansion of CD8+ T cells in HIV-1 infection', Journal of Clinical Investigation, vol. 126, no. 7, pp. 2745-2756. https://doi.org/10.1172/JCI85996
Younes SA, Freeman ML, Mudd JC, Shive CL, Reynaldi A, Panigrahi S et al. IL-15 promotes activation and expansion of CD8+ T cells in HIV-1 infection. Journal of Clinical Investigation. 2016 Jul 1;126(7):2745-2756. https://doi.org/10.1172/JCI85996
Younes, Souheil Antoine ; Freeman, Michael L. ; Mudd, Joseph C. ; Shive, Carey L. ; Reynaldi, Arnold ; Panigrahi, Soumya ; Estes, Jacob ; Deleage, Claire ; Lucero, Carissa ; Anderson, Jodi ; Schacker, Timothy W. ; Davenport, Miles P. ; McCune, Joseph M. ; Hunt, Peter W. ; Lee, Sulggi A. ; Serrano-Villar, Sergio ; Debernardo, Robert L. ; Jacobson, Jeffrey M. ; Canaday, David H. ; Sekaly, Raafick Pierre ; Rodriguez, Benigno ; Sieg, Scott F. ; Lederman, Michael M. / IL-15 promotes activation and expansion of CD8+ T cells in HIV-1 infection. In: Journal of Clinical Investigation. 2016 ; Vol. 126, No. 7. pp. 2745-2756.
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AU - Panigrahi, Soumya

AU - Estes, Jacob

AU - Deleage, Claire

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AU - Anderson, Jodi

AU - Schacker, Timothy W.

AU - Davenport, Miles P.

AU - McCune, Joseph M.

AU - Hunt, Peter W.

AU - Lee, Sulggi A.

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AU - Debernardo, Robert L.

AU - Jacobson, Jeffrey M.

AU - Canaday, David H.

AU - Sekaly, Raafick Pierre

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