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

High Number of Activated CD8+ T Cells Targeting HIV Antigens are Present in Cerebrospinal Fluid in Acute HIV Infection.
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Kessing CF, Spudich S, Valcour V, Cartwright P, Chalermchai T, Fletcher JL, Nichols C, Josey BJ, Slike B, Krebs SJ, Sailsuta N, Lerdlum S, Jagodzinski L, Tipsuk S, Suttichom D, Rattanamanee S, Zetterberg H, Hellmuth J, Phanuphak N, Robb ML, Michael NL, Ananworanich J, Trautmann L,


Kessing CF, Spudich S, Valcour V, Cartwright P, Chalermchai T, Fletcher JL, Nichols C, Josey BJ, Slike B, Krebs SJ, Sailsuta N, Lerdlum S, Jagodzinski L, Tipsuk S, Suttichom D, Rattanamanee S, Zetterberg H, Hellmuth J, Phanuphak N, Robb ML, Michael NL, Ananworanich J, Trautmann L, (click to view)

Kessing CF, Spudich S, Valcour V, Cartwright P, Chalermchai T, Fletcher JL, Nichols C, Josey BJ, Slike B, Krebs SJ, Sailsuta N, Lerdlum S, Jagodzinski L, Tipsuk S, Suttichom D, Rattanamanee S, Zetterberg H, Hellmuth J, Phanuphak N, Robb ML, Michael NL, Ananworanich J, Trautmann L,

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Journal of acquired immune deficiency syndromes (1999) 2017 02 07() doi 10.1097/QAI.0000000000001301

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 is unknown.

METHODS
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).

RESULTS
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.

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 CHI if cART is initiated early.

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