High Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection.

Journal of acquired immune deficiency syndromes (1999) 2017 May 01

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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. 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). 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. 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.

Citation

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 Phanuphak, Merlin L Robb, Nelson L Michael, Jintanat Ananworanich, Lydie Trautmann. High Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV Infection. Journal of acquired immune deficiency syndromes (1999). 2017 May 01;75(1):108-117