High number of activated CD8+ T cells targeting HIV antigens are present in cerebrospinal fluid in acute HIV infection

Cari F. Kessing, Serena Spudich, Victor Valcour, Pearline Cartwright, Thep Chalermchai, James L.K. Fletcher, Hiroshi Takata, Carmen Nichols, Benjamin J. Josey, Bonnie Slike, Shelly J. Krebs, Napapon Sailsuta, Sukalaya Lerdlum, Linda Jagodzinski, Somporn Tipsuk, Duanghathai Suttichom, Somprartthana Rattanamanee, Henrik Zetterberg, Joanna Hellmuth, Nittaya PhanuphakMerlin L. Robb, Nelson L. Michael, Jintanat Ananworanich, Lydie Trautmann

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Background: Central nervous system (CNS) infiltration by CD8+ T cells is associated with neuroinflammation in many neurodegenerative diseases, including HIV-associated dementia. However, the role of CD8+ T cells in the CNS during acute HIV infection (AHI) is unknown. Methods: We analyzed the phenotype, gene expression, T cell receptor (TCR) repertoire, and HIV specificity of CD8+ T cells in cerebrospinal fluid (CSF) of a unique cohort captured during the earliest stages of AHI (n = 26), chronic (n = 23), and uninfected (n = 8). Results: CSF CD8+ T cells were elevated in AHI compared with uninfected controls. The frequency of activated CSF CD8+ T cells positively correlated to CSF HIV RNA and to markers of CNS inflammation. In contrast, activated CSF CD8+ T cells during chronic HIV infection were associated with markers of neurological injury and microglial activation. CSF CD8+ T cells in AHI exhibited increased functional gene expression profiles associated with CD8+ T cells effector function, proliferation, and TCR signaling, a unique restricted TCR Vbeta repertoire and contained HIV-specific CD8+ T cells directed to unique HIV epitopes compared with the periphery. Conclusions: These results suggest that CSF CD8+ T cells in AHI expanding in the CNS are functional and directed against HIV antigens. These cells could thus play a beneficial role protective of injury seen in chronic HIV infection if combination antiretroviral therapy is initiated early.

Original languageEnglish (US)
Pages (from-to)108-117
Number of pages10
JournalJournal of Acquired Immune Deficiency Syndromes
Volume75
Issue number1
DOIs
StatePublished - 2017
Externally publishedYes

Keywords

  • Cytotoxic T lymphocytes
  • HIV
  • HIV-associated neurocognitive disorders
  • HIV-specific CD8+ T cells
  • Neuroinflammation

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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