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

Summary, in English

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.

• Författare: Marcus Buggert; Juliet Frederiksen; Ole Lund; Michael R. Betts; Antonio Biague; Morten Nielsen; Johanna Tauriainen; Hans Norrgren; Patrik Medstrand; Annika C. Karlsson; Marianne Jansson
• Avdelning/ar: Infektionsmedicin; Klinisk virologi, Malmö; Institutionen för laboratoriemedicin; Avdelningen för medicinsk mikrobiologi; HIV-1 och HIV-2 värd interaktioner
• Publiceringsår: 2016-08-11
• Språk: Engelska
• Sidor: 2415-2426
• Publikation/Tidskrift/Serie: AIDS
• Volym: 30
• Issue: 16
• Länkar: http://dx.doi.org/10.1097/QAD.0000000000001223
• Dokumenttyp: Artikel i tidskrift
• Förlag: Lippincott Williams & Wilkins
• Ämne: Infectious Medicine
• Status: Published
• Forskningsgrupp: Clinical Virology, Malmö; HIV-1 and HIV-2 host interactions
• ISBN/ISSN/Övrigt: ISSN: 0269-9370