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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

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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 5

Immune activation is associated with the accumulation of fCD8+ T cells during chronic SIV infection.

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Immune activation is associated with the accumulation of fCD8+ T cells d...
(A) Representative confocal images showing CD20+, CD3+, and CD4+ staining with SIV RNA ISH (RNAscope). Follicular areas from a noninfected, an early chronic, and a late chronic SIV-infected LN are shown. SIV mRNA is shown in red. Scale bars: 50 μm and 10 μm (enlarged images of boxed areas). (B) Pooled data showing the relative frequency of total LN CD8+ T cells in chronically SIV-infected RMs (n = 17) and AGMs (n = 5), expressed as the frequency of total CD3+ T cells. Mann-Whitney U test. (C) Relative appearance of LN CD8+ T cell subsets (top) and frequency of LN CCR7loCD95hi CD8+ T cells (bottom) in chronically SIV-infected RMs (n = 17) and AGMs (n = 5). ***P < 0.0001, by Mann-Whitney U test. (D) Relative frequency of fCD8+ T cells. ***P < 0.0001, by Mann-Whitney U test. (E) Representative confocal images showing B cell follicles and T cell distribution in 2 SIV-infected AGMs. Individual staining and merged images (CD3/CD4 and CD20/Ki67) are shown. Scale bars: 50 μm (top) and 100 μm (bottom). Original magnification, ×20. (F) Confocal images showing the distribution of PD-1hi cells and the presence of CXCL13 in follicular areas from chronically infected RMs (n = 1) and AGMs (n = 2). Two follicles (F1, F2) from each animal are shown. Original magnification, ×40. Scale bars: 20 μm.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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