High Number of Activated CD8+ T Cells Targeting HIV Antigens are Present in Cerebrospinal Fluid in Acute HIV Infection
JAIDS Journal of Acquired Immune Deficiency Syndromes: May 1st, 2017 – Volume 75 – Issue 1 – p 108–117
Cari F. Kessing, PhD, Serena Spudich, MD, Victor Valcour, MD, PhD, Pearline Cartwright, MSc, Thep Chalermchai, MD, James L.K. Fletcher, BM, BCH, Carmen Nichols, PhD, Benjamin J. Josey, PhD, Bonnie Slike, MSc, Shelly J. Krebs, PhD, Napapon Sailsuta, PhD, Sukalaya Lerdlum, MD, Linda Jagodzinski, PhD, Somporn Tipsuk, BNS, Duanghathai Suttichom, MNS, Somprartthana Rattanamanee, MSc, Henrik Zetterberg, MD, PhD, Joanna Hellmuth, MD, MHS, Nittaya Phanuphak, MD, PhD, Merlin L. Robb, MD, Nelson L. Michael, MD, PhD, Jintanat Ananworanich, MD, PhD, and Lydie Trautmann, PhD
Quansys Products Used:
Q-Plex ELISA, Q-View Software
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 is unknown.
We analyzed the phenotype, gene expression, TCR repertoire and HIV-specificity of CD8+ T cells in cerebrospinal fluid (CSF) of a unique cohort captured during the earliest stages of acute HIV infection (AHI) (n=26), chronic (n=23), and uninfected (n=8).
CSF CD8+ T cells were elevated in AHI compared to 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 infection (CHI) 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 to the periphery.
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 CHI if cART is initiated early.