Header

UZH-Logo

Maintenance Infos

CD8+ T cells are activated in an antigen-independent manner in HIV-infected individuals


Bastidas, Sonia; Graw, Frederik; Smith, Miranda Z; Kuster, Herbert; Günthard, Huldrych F; Oxenius, Annette (2014). CD8+ T cells are activated in an antigen-independent manner in HIV-infected individuals. Journal of Immunology, 192(4):1732-1744.

Abstract

Hyperactivation of T cells, particularly of CD8(+) T cells, is a hallmark of chronic HIV 1 (HIV-1) infection. Little is known about the antigenic specificities and the mechanisms by which HIV-1 causes activation of CD8(+) T cells during chronic infection. We report that CD8(+) T cells were activated during in vivo HIV-1 replication irrespective of their Ag specificity. Cytokines present during untreated HIV-1 infection, most prominently IL-15, triggered proliferation and expression of activation markers in CD8(+) T cells, but not CD4(+) T cells, in the absence of TCR stimulation. Moreover, LPS or HIV-1-activated dendritic cells (DCs) stimulated CD8(+) T cells in an IL-15-dependent but Ag-independent manner, and IL-15 expression was highly increased in DCs isolated from viremic HIV-1 patients, suggesting that CD8(+) T cells are activated by inflammatory cytokines in untreated HIV-1 patients independent of Ag specificity. This finding contrasts with CD4(+) T cells whose in vivo activation seems biased toward specificities for persistent Ags. These observations explain the higher abundance of activated CD8(+) T cells compared with CD4(+) T cells in untreated HIV-1 infection.

Abstract

Hyperactivation of T cells, particularly of CD8(+) T cells, is a hallmark of chronic HIV 1 (HIV-1) infection. Little is known about the antigenic specificities and the mechanisms by which HIV-1 causes activation of CD8(+) T cells during chronic infection. We report that CD8(+) T cells were activated during in vivo HIV-1 replication irrespective of their Ag specificity. Cytokines present during untreated HIV-1 infection, most prominently IL-15, triggered proliferation and expression of activation markers in CD8(+) T cells, but not CD4(+) T cells, in the absence of TCR stimulation. Moreover, LPS or HIV-1-activated dendritic cells (DCs) stimulated CD8(+) T cells in an IL-15-dependent but Ag-independent manner, and IL-15 expression was highly increased in DCs isolated from viremic HIV-1 patients, suggesting that CD8(+) T cells are activated by inflammatory cytokines in untreated HIV-1 patients independent of Ag specificity. This finding contrasts with CD4(+) T cells whose in vivo activation seems biased toward specificities for persistent Ags. These observations explain the higher abundance of activated CD8(+) T cells compared with CD4(+) T cells in untreated HIV-1 infection.

Statistics

Citations

14 citations in Web of Science®
13 citations in Scopus®
Google Scholar™

Altmetrics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:15 February 2014
Deposited On:16 Dec 2014 13:24
Last Modified:05 Apr 2016 18:37
Publisher:American Association of Immunologists
ISSN:0022-1767
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.4049/jimmunol.1302027
PubMed ID:24446519

Download

Full text not available from this repository.
View at publisher

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations