Simian Immunodeficiency Virus Infects Follicular Helper CD4 T Cells in Lymphoid Tissues during Pathogenic Infection of Pigtail Macaques
Identifieur interne : 004482 ( Main/Exploration ); précédent : 004481; suivant : 004483Simian Immunodeficiency Virus Infects Follicular Helper CD4 T Cells in Lymphoid Tissues during Pathogenic Infection of Pigtail Macaques
Auteurs : Yin Xu [Australie] ; Chris Weatherall [Australie] ; Michelle Bailey [Australie] ; Sheilajen Alcantara [Australie] ; Robert De Rose [Australie] ; Jerome Estaquier [France, Canada] ; Kim Wilson [Australie] ; Kazuo Suzuki [Australie] ; Jacques Corbeil [Canada] ; David A. Cooper [Australie] ; Stephen J. Kent [Australie] ; Anthony D. Kelleher [Australie] ; John Zaunders [Australie]Source :
- Journal of Virology [ 0022-538X ] ; 2013.
Abstract
T follicular helper (Tfh) cells are a specialized subset of memory CD4+ T cells that are found exclusively within the germinal centers of secondary lymphoid tissues and are important for adaptive antibody responses and B cell memory. Tfh cells do not express CCR5, the primary entry coreceptor for both human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), and therefore, we hypothesized that these cells would avoid infection. We studied lymph nodes and spleens from pigtail macaques infected with pathogenic strain SIVmac239 or SIVmac251, to investigate the susceptibility of Tfh cells to SIV infection. Pigtail macaque PD-1high CD127low memory CD4+ T cells have a phenotype comparable to that of human Tfh cells, expressing high levels of CXCR5, interleukin-21 (IL-21), Bcl-6, and inducible T cell costimulator (ICOS). As judged by either proviral DNA or cell-associated viral RNA measurements, macaque Tfh cells were infected with SIV at levels comparable to those in other CD4+ memory T cells. Infection of macaque Tfh cells was evident within weeks of inoculation, yet we confirmed that Tfh cells do not express CCR5 or either of the well-known alternative SIV coreceptors, CXCR6 and GPR15. Mutations in the SIV envelope gp120 region occurred in chronically infected macaques but were uniform across each T cell subset investigated, indicating that the viruses used the same coreceptors to enter different cell subsets. Early infection of Tfh cells represents an unexpected focus of viral infection. Infection of Tfh cells does not interrupt antibody production but may be a factor that limits the quality of antibody responses and has implications for assessing the size of the viral reservoir.
Url:
DOI: 10.1128/JVI.02497-12
PubMed: 23325697
PubMed Central: 3624224
Affiliations:
- Australie, Canada, France
- Victoria (État), Île-de-France
- Melbourne, Paris
- Université Paris-Descartes, Université de Melbourne
Links toward previous steps (curation, corpus...)
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Le document en format XML
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<front><div type="abstract" xml:lang="en"><p>T follicular helper (Tfh) cells are a specialized subset of memory CD4<sup>+</sup>
T cells that are found exclusively within the germinal centers of secondary lymphoid tissues and are important for adaptive antibody responses and B cell memory. Tfh cells do not express CCR5, the primary entry coreceptor for both human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), and therefore, we hypothesized that these cells would avoid infection. We studied lymph nodes and spleens from pigtail macaques infected with pathogenic strain SIVmac239 or SIVmac251, to investigate the susceptibility of Tfh cells to SIV infection. Pigtail macaque PD-1<sup>high</sup>
CD127<sup>low</sup>
memory CD4<sup>+</sup>
T cells have a phenotype comparable to that of human Tfh cells, expressing high levels of CXCR5, interleukin-21 (IL-21), Bcl-6, and inducible T cell costimulator (ICOS). As judged by either proviral DNA or cell-associated viral RNA measurements, macaque Tfh cells were infected with SIV at levels comparable to those in other CD4<sup>+</sup>
memory T cells. Infection of macaque Tfh cells was evident within weeks of inoculation, yet we confirmed that Tfh cells do not express CCR5 or either of the well-known alternative SIV coreceptors, CXCR6 and GPR15. Mutations in the SIV envelope gp120 region occurred in chronically infected macaques but were uniform across each T cell subset investigated, indicating that the viruses used the same coreceptors to enter different cell subsets. Early infection of Tfh cells represents an unexpected focus of viral infection. Infection of Tfh cells does not interrupt antibody production but may be a factor that limits the quality of antibody responses and has implications for assessing the size of the viral reservoir.</p>
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<name sortKey="Alcantara, Sheilajen" sort="Alcantara, Sheilajen" uniqKey="Alcantara S" first="Sheilajen" last="Alcantara">Sheilajen Alcantara</name>
<name sortKey="Bailey, Michelle" sort="Bailey, Michelle" uniqKey="Bailey M" first="Michelle" last="Bailey">Michelle Bailey</name>
<name sortKey="Cooper, David A" sort="Cooper, David A" uniqKey="Cooper D" first="David A." last="Cooper">David A. Cooper</name>
<name sortKey="Cooper, David A" sort="Cooper, David A" uniqKey="Cooper D" first="David A." last="Cooper">David A. Cooper</name>
<name sortKey="De Rose, Robert" sort="De Rose, Robert" uniqKey="De Rose R" first="Robert" last="De Rose">Robert De Rose</name>
<name sortKey="Kelleher, Anthony D" sort="Kelleher, Anthony D" uniqKey="Kelleher A" first="Anthony D." last="Kelleher">Anthony D. Kelleher</name>
<name sortKey="Kelleher, Anthony D" sort="Kelleher, Anthony D" uniqKey="Kelleher A" first="Anthony D." last="Kelleher">Anthony D. Kelleher</name>
<name sortKey="Kent, Stephen J" sort="Kent, Stephen J" uniqKey="Kent S" first="Stephen J." last="Kent">Stephen J. Kent</name>
<name sortKey="Suzuki, Kazuo" sort="Suzuki, Kazuo" uniqKey="Suzuki K" first="Kazuo" last="Suzuki">Kazuo Suzuki</name>
<name sortKey="Weatherall, Chris" sort="Weatherall, Chris" uniqKey="Weatherall C" first="Chris" last="Weatherall">Chris Weatherall</name>
<name sortKey="Wilson, Kim" sort="Wilson, Kim" uniqKey="Wilson K" first="Kim" last="Wilson">Kim Wilson</name>
<name sortKey="Zaunders, John" sort="Zaunders, John" uniqKey="Zaunders J" first="John" last="Zaunders">John Zaunders</name>
<name sortKey="Zaunders, John" sort="Zaunders, John" uniqKey="Zaunders J" first="John" last="Zaunders">John Zaunders</name>
</country>
<country name="France"><region name="Île-de-France"><name sortKey="Estaquier, Jerome" sort="Estaquier, Jerome" uniqKey="Estaquier J" first="Jerome" last="Estaquier">Jerome Estaquier</name>
</region>
</country>
<country name="Canada"><noRegion><name sortKey="Estaquier, Jerome" sort="Estaquier, Jerome" uniqKey="Estaquier J" first="Jerome" last="Estaquier">Jerome Estaquier</name>
</noRegion>
<name sortKey="Corbeil, Jacques" sort="Corbeil, Jacques" uniqKey="Corbeil J" first="Jacques" last="Corbeil">Jacques Corbeil</name>
</country>
</tree>
</affiliations>
</record>
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