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.
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Research Article AIDS/HIV Immunology Article has an altmetric score of 2

Accumulation of follicular CD8+ T cells in pathogenic SIV infection

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

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Figure 2

SIV-specific CD8+ T cells with a follicular phenotype do not preferentially accumulate in LNs during chronic SIV infection.

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SIV-specific CD8+ T cells with a follicular phenotype do not preferentia...
(A) Pooled data showing the frequency of TNF-α+ CCR7loCD95hi CD8+ T cells in PBMC (n = 6 responders) and LN (n = 8 responders) samples after short ex vivo stimulation with Gag (circles) or Env (triangles) peptide pools. Matching samples are highlighted with paired colors. Mann-Whitney U test. (B) Frequency of TNF-α+ CD8+ T cells in non-fCD8+ (n = 9 responders) and fCD8+ (n = 9 responders) compartments. Matching samples are highlighted with paired colors. Mann-Whitney U test. The polyfunctionality of virus-specific CD8+ T cell responses after short ex vivo stimulation (Gag or Env peptide pools) in paired samples of (C) LN cells (n = 12 responders) and PBMCs (n = 9 responders) and (D) paired LN non-fCD8+ and fCD8+ T cells. #P < 0.05, by Wilcoxon signed-rank test. (E) Relative frequency of tetramer+, SIV-specific CD8+ T cells in PBMC (n = 5) and LN (n = 5) samples and LN non-fCD8+ and fCD8+ T cell compartments. Representative flow cytometric plots for CM9+ (Gag) and TL8+ (Tat) fCD8+ T cells from 2 animals (LNs) are also shown. All results are from chronically SIV-infected animals. A Mann-Whitney U test was used for unpaired comparisons and a Wilcoxon test for paired comparisons.