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 6

Accumulation of functional monocytes in proximity to follicular areas during SIV infection.

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Accumulation of functional monocytes in proximity to follicular areas du...
(A) Representative flow cytometric plots showing the gating scheme for identification of monocyte subsets and pooled data showing the relative frequency of CD14hiCD16hi monocytes in LNs from noninfected RMs (n = 11), chronically infected RMs (n = 11), and chronically infected AGMs (n = 5). *P < 0.05, by Mann-Whitney U test. (B) Linear regression analysis showing the association between the frequency of LN CD14hiCD16hi monocytes and LN total CD8+ T cells. (C) Representative confocal images showing the distribution of monocytes (CD163hi, in red) and granulocytes (MPOhi, in green) in LN tissues from noninfected and acutely and chronically SIV-infected RMs. Two zoomed areas close to the B cell follicle (defined by CD20 and Ki67 expression) from each animal are also shown. Scale bars: 400μm (top two), 200 μm (third row), and 300 μm (lower); enlarged 50 μm; 40 μm (second row, right). Original magnification, ×20. (D) Pooled data showing CXCL10 production by CD14hiCD16hi and CD14hiCD16lo monocytes (flow cytometric intracellular staining analysis) after short in vitro stimulation with either IFN-α or IFN-γ. Cells from noninfected (n = 8) and chronically SIV-infected (n = 8) RMs were analyzed. *P < 0.05, by Mann-Whitney U test. (E) Relative frequency of LN CD14hiCD16hi monocytes before and after cART from RMs treated during early (n = 5) or late (n = 8) SIV infection. Mann-Whitney U test for unpaired comparisons and Wilcoxon test for paired comparisons.