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CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection

Buggert, Marcus; Frederiksen, Juliet; Lund, Ole; Betts, Michael R.; Biague, Antonio; Nielsen, Morten; Tauriainen, Johanna; Norrgren, Hans LU ; Medstrand, Patrik LU and Karlsson, Annika C., et al. (2016) In AIDS 30(16). p.2415-2426
Abstract

OBJECTIVE:: HIV-2 represents an attenuated form of HIV, where many infected individuals remain “aviremic” without antiretroviral therapy (ART). However, aviremic HIV-2 disease progression exits, and in the current study we therefore aimed to examine if specific pathological characteristics of CD4+ T cells are linked to such outcome. DESIGN:: HIV-seronegative (n=25), HIV-1 (n?=?33), HIV-2 (n?=?39, of whom 26 were aviremic), and HIV-1/2 dually (HIV-D) (n?=?13) infected subjects were enrolled from an occupational cohort in Guinea-Bissau. METHODS:: CD4+ T cell differentiation, activation, exhaustion, senescence, and transcription factors were assessed by polychromatic flow cytometry. Multidimensional clustering bioinformatic tools were used... (More)

OBJECTIVE:: HIV-2 represents an attenuated form of HIV, where many infected individuals remain “aviremic” without antiretroviral therapy (ART). However, aviremic HIV-2 disease progression exits, and in the current study we therefore aimed to examine if specific pathological characteristics of CD4+ T cells are linked to such outcome. DESIGN:: HIV-seronegative (n=25), HIV-1 (n?=?33), HIV-2 (n?=?39, of whom 26 were aviremic), and HIV-1/2 dually (HIV-D) (n?=?13) infected subjects were enrolled from an occupational cohort in Guinea-Bissau. METHODS:: CD4+ T cell differentiation, activation, exhaustion, senescence, and transcription factors were assessed by polychromatic flow cytometry. Multidimensional clustering bioinformatic tools were used to identify CD4+ T cell subpopulations linked to infection type and disease stage. RESULTS:: HIV-2-infected individuals had early- and late-differentiated CD4+ T cell clusters with lower activation (CD38+HLA-DR+) and exhaustion (PD-1) than HIV-1 and HIV-D-infected subjects. We also noted that aviremic HIV-2-infected individuals possessed fewer CD4+ T cells with pathological signs compared to other HIV-infected groups. Still, compared to HIV-seronegatives, aviremic HIV-2-infected subjects had T-bet+ CD4+ T cells that showed elevated immune activation/exhaustion, and particularly the frequencies of PD-1+ cells were associated with suboptimal percentage of CD4+ T cells. CONCLUSIONS:: Increased frequencies of CD4+ T cells with an activated/exhausted phenotype correlate with exacerbated immunodeficiency in aviremic HIV-2-infected individuals. Thus, these findings encourage studies on the introduction of ART also to individuals with aviremic HIV-2 infection.

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publication status
published
subject
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AIDS
volume
30
issue
16
pages
2415 - 2426
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:84981736213
ISSN
0269-9370
DOI
10.1097/QAD.0000000000001223
language
English
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yes
id
0ea70304-ed71-482c-926f-54ab6e4e1214
date added to LUP
2016-09-20 13:51:04
date last changed
2017-06-25 04:54:10
@article{0ea70304-ed71-482c-926f-54ab6e4e1214,
  abstract     = {<p>OBJECTIVE:: HIV-2 represents an attenuated form of HIV, where many infected individuals remain “aviremic” without antiretroviral therapy (ART). However, aviremic HIV-2 disease progression exits, and in the current study we therefore aimed to examine if specific pathological characteristics of CD4+ T cells are linked to such outcome. DESIGN:: HIV-seronegative (n=25), HIV-1 (n?=?33), HIV-2 (n?=?39, of whom 26 were aviremic), and HIV-1/2 dually (HIV-D) (n?=?13) infected subjects were enrolled from an occupational cohort in Guinea-Bissau. METHODS:: CD4+ T cell differentiation, activation, exhaustion, senescence, and transcription factors were assessed by polychromatic flow cytometry. Multidimensional clustering bioinformatic tools were used to identify CD4+ T cell subpopulations linked to infection type and disease stage. RESULTS:: HIV-2-infected individuals had early- and late-differentiated CD4+ T cell clusters with lower activation (CD38+HLA-DR+) and exhaustion (PD-1) than HIV-1 and HIV-D-infected subjects. We also noted that aviremic HIV-2-infected individuals possessed fewer CD4+ T cells with pathological signs compared to other HIV-infected groups. Still, compared to HIV-seronegatives, aviremic HIV-2-infected subjects had T-bet+ CD4+ T cells that showed elevated immune activation/exhaustion, and particularly the frequencies of PD-1+ cells were associated with suboptimal percentage of CD4+ T cells. CONCLUSIONS:: Increased frequencies of CD4+ T cells with an activated/exhausted phenotype correlate with exacerbated immunodeficiency in aviremic HIV-2-infected individuals. Thus, these findings encourage studies on the introduction of ART also to individuals with aviremic HIV-2 infection.</p>},
  author       = {Buggert, Marcus and Frederiksen, Juliet and Lund, Ole and Betts, Michael R. and Biague, Antonio and Nielsen, Morten and Tauriainen, Johanna and Norrgren, Hans and Medstrand, Patrik and Karlsson, Annika C. and Jansson, Marianne},
  issn         = {0269-9370},
  language     = {eng},
  month        = {08},
  number       = {16},
  pages        = {2415--2426},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {AIDS},
  title        = {CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection},
  url          = {http://dx.doi.org/10.1097/QAD.0000000000001223},
  volume       = {30},
  year         = {2016},
}