Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
Accumulation of follicular CD8+ T cells in pathogenic SIV infection
Sara Ferrando-Martinez, … , Constantinos Petrovas, Richard A. Koup
Sara Ferrando-Martinez, … , Constantinos Petrovas, Richard A. Koup
Published April 16, 2018
Citation Information: J Clin Invest. 2018;128(5):2089-2103. https://doi.org/10.1172/JCI96207.
View: Text | PDF
Research Article AIDS/HIV Immunology

Accumulation of follicular CD8+ T cells in pathogenic SIV infection

  • Text
  • PDF
Abstract

LN follicles constitute major reservoir sites for HIV/SIV persistence. Cure strategies could benefit from the characterization of CD8+ T cells able to access and eliminate HIV-infected cells from these areas. In this study, we provide a comprehensive analysis of the phenotype, frequency, localization, and functionality of follicular CD8+ T cells (fCD8+) in SIV-infected nonhuman primates. Although disorganization of follicles was a major factor, significant accumulation of fCD8+ cells during chronic SIV infection was also observed in intact follicles, but only in pathogenic SIV infection. In line with this, tissue inflammatory mediators were strongly associated with the accumulation of fCD8+ cells, pointing to tissue inflammation as a major factor in this process. These fCD8+ cells have cytolytic potential and can be redirected to target and kill HIV-infected cells using bispecific antibodies. Altogether, our data support the use of SIV infection to better understand the dynamics of fCD8+ cells and to develop bispecific antibodies as a strategy for virus eradication.

Authors

Sara Ferrando-Martinez, Eirini Moysi, Amarendra Pegu, Sarah Andrews, Krystelle Nganou Makamdop, David Ambrozak, Adrian B. McDermott, David Palesch, Mirko Paiardini, George N. Pavlakis, Jason M. Brenchley, Daniel Douek, John R. Mascola, Constantinos Petrovas, Richard A. Koup

×

Figure 1

fCD8+ T cells accumulate in LNs during chronic SIV infection.

Options: View larger image (or click on image) Download as PowerPoint
fCD8+ T cells accumulate in LNs during chronic SIV infection.
(A) Gating...
(A) Gating strategy for CCR7loCD95hiCXCR5hi fCD8+ cells. (B) Flow cytometric pooled data showing the relative frequency of fCD8+ T cells in noninfected (n = 16 SIV–), acute SIV+ (day 14, n = 10), early chronic SIV+ (day 45, n = 8), and chronic SIV+ (>6 months, n = 17) RMs. *P < 0.05 and ***P < 0.0001, by Mann-Whitney U test. (C) Representative example of histocytometric analysis of follicular cells from 1 chronically SIV-infected animal (7 different samples were analyzed using this method). GCs were defined by CD20+Ki67+ coexpression, and CD4+ (CD3+CD4+) and CD8+ (CD3+CD4–) T cells were quantified within each GC. A representative confocal image and its reconstruction using histocytometry are shown. Scale bar: 400 μm. (D) Histocytometric pooled data showing the relative frequency and actual numbers (per μm2) of CD8+ T cells within GCs. Each point represents an individual GC. Different symbols represent different samples (n = 2 SIV–; n = 2 acute SIV+, n = 3 chronic SIV+). **P < 0.001 and ***P < 0.0001, by Mann-Whitney U test. (E) Pooled data showing the relative frequency and actual numbers (per μm2) of CD8+ T cells within intact and disorganized GCs from chronically SIV-infected animals (n = 5). Data from SIV– (n = 2) and acute SIV-infected animals (n = 2) are also shown. Each point represents an individual GC, and different symbols represent different LN samples. **P < 0.001 and ***P < 0.0001, by Mann-Whitney U test.
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts