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High Number of Activated CD8+ T Cells Targeting HIV Antigens Are Present in Cerebrospinal Fluid in Acute HIV
Cari F Kessing1, Serena Spudich, Victor Valcour
1*Vaccine and Gene Therapy Institute-Florida, Port St Lucie, FL; †Currently, Cari F. Kessing, Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL; Pearline Cartwright, Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH; Carmen Nichols and Benjamin J. Josey, Cell Therapies Institute, Nova Southeastern University, FL; ‡Yale University School of Medicine, New Haven, CT; §Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA; ‖SEARCH, The Thai Red Cross AIDS Research Center, Bangkok, Thailand; ¶Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD; #U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD; **University of Hawaii, Honolulu, HI; ††Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; ‡‡Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; and §§University College London Institute of Neurology, Queen Square, London, United Kingdom.
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.
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