CD25+ FoxP3+ memory CD4 T cells are frequent targets of HIV infection in vivo

Mkunde Chachage, Georgios Pollakis, Edmund Osei Kuffour, Kerstin Haase, Asli Bauer, Yuka Nadai, Lilli Podola, Petra Clowes, Matthias Schiemann, Lynette Henkel, Dieter Hoffmann, Sarah Joseph, Sabin Bhuju, Leonard Maboko, Fred Stephen Sarfo, Kirsten Eberhardt, Michael Hoelscher, Torsten Feldt, Elmar Saathoff, Christof Geldmacher

Research output: Contribution to journalArticle

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Abstract

Interleukin 2 (IL-2) signaling through the IL-2 receptor alpha chain (CD25) facilitates HIV replication in vitro and facilitates homeostatic proliferation of CD25+ FoxP3+ CD4+ T cells. CD25+ FoxP3+ CD4+ T cells may therefore constitute a suitable subset for HIV infection and plasma virion production. CD25+ FoxP3+ CD4+ T cell frequencies, absolute numbers, and the expression of CCR5 and cell cycle marker Ki67 were studied in peripheral blood from HIV+ and HIV- study volunteers. Different memory CD4+ T cell subsets were then sorted for quantification of cell-associated HIV DNA and phylogenetic analyses of the highly variable EnvV1V3 region in comparison to plasma-derived virus sequences. In HIV+ subjects, 51% (median) of CD25+ FoxP3+ CD4+ T cells expressed the HIV coreceptor CCR5. Very high frequencies of Ki67+ cells were detected in CD25+ FoxP3+ memory CD4+ T cells (median, 27.6%) in comparison to CD25- FoxP3- memory CD4+ T cells (median, 4.1%; P < 0.0001). HIV DNA content was 15-fold higher in CD25+ FoxP3+ memory CD4+ T cells than in CD25- FoxP3- T cells (P = .003). EnvV1V3 sequences derived from CD25+ FoxP3+ memory CD4+ T cells did not preferentially cluster with plasma-derived sequences. Quasi-identical cell-plasma sequence pairs were rare, and their proportion decreased with the estimated HIV infection duration. These data suggest that specific cellular characteristics of CD25+ FoxP3+ memory CD4+ T cells might facilitate efficient HIV infection in vivo and passage of HIV DNA to cell progeny in the absence of active viral replication. The contribution of this cell population to plasma virion production remains unclear.

LanguageEnglish (US)
Pages8954-8967
Number of pages14
JournalJournal of Virology
Volume90
Issue number20
DOIs
StatePublished - Jan 1 2016

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HIV infections
HIV Infections
T-lymphocytes
T-Lymphocytes
HIV
Virion
interleukin-2
virion
DNA
Interleukin-2 Receptor alpha Subunit
cells
T-Lymphocyte Subsets
plasma cells
Plasma Cells
virus replication
Interleukin-2
Volunteers
Cell Cycle
volunteers
cell cycle

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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Chachage, M., Pollakis, G., Kuffour, E. O., Haase, K., Bauer, A., Nadai, Y., ... Geldmacher, C. (2016). CD25+ FoxP3+ memory CD4 T cells are frequent targets of HIV infection in vivo. Journal of Virology, 90(20), 8954-8967. DOI: 10.1128/JVI.00612-16

CD25+ FoxP3+ memory CD4 T cells are frequent targets of HIV infection in vivo. / Chachage, Mkunde; Pollakis, Georgios; Kuffour, Edmund Osei; Haase, Kerstin; Bauer, Asli; Nadai, Yuka; Podola, Lilli; Clowes, Petra; Schiemann, Matthias; Henkel, Lynette; Hoffmann, Dieter; Joseph, Sarah; Bhuju, Sabin; Maboko, Leonard; Sarfo, Fred Stephen; Eberhardt, Kirsten; Hoelscher, Michael; Feldt, Torsten; Saathoff, Elmar; Geldmacher, Christof.

In: Journal of Virology, Vol. 90, No. 20, 01.01.2016, p. 8954-8967.

Research output: Contribution to journalArticle

Chachage, M, Pollakis, G, Kuffour, EO, Haase, K, Bauer, A, Nadai, Y, Podola, L, Clowes, P, Schiemann, M, Henkel, L, Hoffmann, D, Joseph, S, Bhuju, S, Maboko, L, Sarfo, FS, Eberhardt, K, Hoelscher, M, Feldt, T, Saathoff, E & Geldmacher, C 2016, 'CD25+ FoxP3+ memory CD4 T cells are frequent targets of HIV infection in vivo' Journal of Virology, vol. 90, no. 20, pp. 8954-8967. DOI: 10.1128/JVI.00612-16
Chachage M, Pollakis G, Kuffour EO, Haase K, Bauer A, Nadai Y et al. CD25+ FoxP3+ memory CD4 T cells are frequent targets of HIV infection in vivo. Journal of Virology. 2016 Jan 1;90(20):8954-8967. Available from, DOI: 10.1128/JVI.00612-16
Chachage, Mkunde ; Pollakis, Georgios ; Kuffour, Edmund Osei ; Haase, Kerstin ; Bauer, Asli ; Nadai, Yuka ; Podola, Lilli ; Clowes, Petra ; Schiemann, Matthias ; Henkel, Lynette ; Hoffmann, Dieter ; Joseph, Sarah ; Bhuju, Sabin ; Maboko, Leonard ; Sarfo, Fred Stephen ; Eberhardt, Kirsten ; Hoelscher, Michael ; Feldt, Torsten ; Saathoff, Elmar ; Geldmacher, Christof. / CD25+ FoxP3+ memory CD4 T cells are frequent targets of HIV infection in vivo. In: Journal of Virology. 2016 ; Vol. 90, No. 20. pp. 8954-8967
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abstract = "Interleukin 2 (IL-2) signaling through the IL-2 receptor alpha chain (CD25) facilitates HIV replication in vitro and facilitates homeostatic proliferation of CD25+ FoxP3+ CD4+ T cells. CD25+ FoxP3+ CD4+ T cells may therefore constitute a suitable subset for HIV infection and plasma virion production. CD25+ FoxP3+ CD4+ T cell frequencies, absolute numbers, and the expression of CCR5 and cell cycle marker Ki67 were studied in peripheral blood from HIV+ and HIV- study volunteers. Different memory CD4+ T cell subsets were then sorted for quantification of cell-associated HIV DNA and phylogenetic analyses of the highly variable EnvV1V3 region in comparison to plasma-derived virus sequences. In HIV+ subjects, 51{\%} (median) of CD25+ FoxP3+ CD4+ T cells expressed the HIV coreceptor CCR5. Very high frequencies of Ki67+ cells were detected in CD25+ FoxP3+ memory CD4+ T cells (median, 27.6{\%}) in comparison to CD25- FoxP3- memory CD4+ T cells (median, 4.1{\%}; P < 0.0001). HIV DNA content was 15-fold higher in CD25+ FoxP3+ memory CD4+ T cells than in CD25- FoxP3- T cells (P = .003). EnvV1V3 sequences derived from CD25+ FoxP3+ memory CD4+ T cells did not preferentially cluster with plasma-derived sequences. Quasi-identical cell-plasma sequence pairs were rare, and their proportion decreased with the estimated HIV infection duration. These data suggest that specific cellular characteristics of CD25+ FoxP3+ memory CD4+ T cells might facilitate efficient HIV infection in vivo and passage of HIV DNA to cell progeny in the absence of active viral replication. The contribution of this cell population to plasma virion production remains unclear.",
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