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Reversible Reprogramming of Circulating Memory T Follicular Helper Cell Function during Chronic HIV Infection.

Publication ,  Journal Article
Cubas, R; van Grevenynghe, J; Wills, S; Kardava, L; Santich, BH; Buckner, CM; Muir, R; Tardif, V; Nichols, C; Procopio, F; He, Z; Metcalf, T ...
Published in: J Immunol
December 15, 2015

Despite the overwhelming benefits of antiretroviral therapy (ART) in curtailing viral load in HIV-infected individuals, ART does not fully restore cellular and humoral immunity. HIV-infected individuals under ART show reduced responses to vaccination and infections and are unable to mount an effective antiviral immune response upon ART cessation. Many factors contribute to these defects, including persistent inflammation, especially in lymphoid tissues, where T follicular helper (Tfh) cells instruct and help B cells launch an effective humoral immune response. In this study we investigated the phenotype and function of circulating memory Tfh cells as a surrogate of Tfh cells in lymph nodes and found significant impairment of this cell population in chronically HIV-infected individuals, leading to reduced B cell responses. We further show that these aberrant memory Tfh cells exhibit an IL-2-responsive gene signature and are more polarized toward a Th1 phenotype. Treatment of functional memory Tfh cells with IL-2 was able to recapitulate the detrimental reprogramming. Importantly, this defect was reversible, as interfering with the IL-2 signaling pathway helped reverse the abnormal differentiation and improved Ab responses. Thus, reversible reprogramming of memory Tfh cells in HIV-infected individuals could be used to enhance Ab responses. Altered microenvironmental conditions in lymphoid tissues leading to altered Tfh cell differentiation could provide one explanation for the poor responsiveness of HIV-infected individuals to new Ags. This explanation has important implications for the development of therapeutic interventions to enhance HIV- and vaccine-mediated Ab responses in patients under ART.

Duke Scholars

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

December 15, 2015

Volume

195

Issue

12

Start / End Page

5625 / 5636

Location

United States

Related Subject Headings

  • Young Adult
  • T-Lymphocytes, Helper-Inducer
  • Signal Transduction
  • Middle Aged
  • Interleukin-2
  • Immunology
  • Immunologic Memory
  • Humans
  • HIV Infections
  • HIV
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Cubas, R., van Grevenynghe, J., Wills, S., Kardava, L., Santich, B. H., Buckner, C. M., … Haddad, E. K. (2015). Reversible Reprogramming of Circulating Memory T Follicular Helper Cell Function during Chronic HIV Infection. J Immunol, 195(12), 5625–5636. https://doi.org/10.4049/jimmunol.1501524
Cubas, Rafael, Julien van Grevenynghe, Saintedym Wills, Lela Kardava, Brian H. Santich, Clarisa M. Buckner, Roshell Muir, et al. “Reversible Reprogramming of Circulating Memory T Follicular Helper Cell Function during Chronic HIV Infection.J Immunol 195, no. 12 (December 15, 2015): 5625–36. https://doi.org/10.4049/jimmunol.1501524.
Cubas R, van Grevenynghe J, Wills S, Kardava L, Santich BH, Buckner CM, et al. Reversible Reprogramming of Circulating Memory T Follicular Helper Cell Function during Chronic HIV Infection. J Immunol. 2015 Dec 15;195(12):5625–36.
Cubas, Rafael, et al. “Reversible Reprogramming of Circulating Memory T Follicular Helper Cell Function during Chronic HIV Infection.J Immunol, vol. 195, no. 12, Dec. 2015, pp. 5625–36. Pubmed, doi:10.4049/jimmunol.1501524.
Cubas R, van Grevenynghe J, Wills S, Kardava L, Santich BH, Buckner CM, Muir R, Tardif V, Nichols C, Procopio F, He Z, Metcalf T, Ghneim K, Locci M, Ancuta P, Routy J-P, Trautmann L, Li Y, McDermott AB, Koup RA, Petrovas C, Migueles SA, Connors M, Tomaras GD, Moir S, Crotty S, Haddad EK. Reversible Reprogramming of Circulating Memory T Follicular Helper Cell Function during Chronic HIV Infection. J Immunol. 2015 Dec 15;195(12):5625–5636.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

December 15, 2015

Volume

195

Issue

12

Start / End Page

5625 / 5636

Location

United States

Related Subject Headings

  • Young Adult
  • T-Lymphocytes, Helper-Inducer
  • Signal Transduction
  • Middle Aged
  • Interleukin-2
  • Immunology
  • Immunologic Memory
  • Humans
  • HIV Infections
  • HIV