Open AccessNeurocognitive decline in HIV patients is associated with ongoing T‐cell activation in the cerebrospinal fluid
Author(s) -
Grauer Oliver M.,
Reichelt Doris,
Grüneberg Ute,
Lohmann Hubertus,
SchneiderHohendorf Tilman,
SchulteMecklenbeck Andreas,
Gross Catharina C.,
Meuth Sven G.,
Wiendl Heinz,
Husstedt Ingo W.
Publication year - 2015
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.227
Subject(s) - neurocognitive , cd8 , medicine , cerebrospinal fluid , cart , flow cytometry , t cell , immune system , immunology , peripheral blood mononuclear cell , biology , in vitro , psychiatry , mechanical engineering , biochemistry , cognition , engineering
Objective HIV ‐associated neurocognitive disorders ( HAND ) remain a challenge despite combination antiretroviral therapy ( cART ). Immune cell activation has been implicated to play a major role in the development of HAND . Methods In this study, we used multicolor flow cytometry on peripheral blood ( PB ) and cerebrospinal fluid ( CSF ) samples to determine the expression of HLA ‐ DR and programmed death‐1 ( PD ‐1) on CD 4+ and CD 8+ T cells in patients with chronic HIV infection. Expression levels were correlated with HI virus load in PB and CSF , classification of HAND and severity of magnetic resonance imaging ( MRI ) signal abnormalities. Results In a cohort of 86 HIV patients we found that the grade of neurocognitive impairment and the severity of MRI signal abnormalities correlated with decreasing CD 4/ CD 8‐ratios and increased frequencies of HLA ‐ DR expressing CD 4+ and CD 8+ T cells reaching the highest values in the CSF samples. Importantly, HLA ‐ DR upregulation was still detectable in virologically suppressed HIV patients. Further, T‐cell subpopulation analysis of 40 HIV patients showed a significant shift from naïve to effector memory ( EM ) T cells that was negatively correlated with the grade of neurocognitive impairment in the PB samples. Moreover, PD ‐1 was significantly increased on CD 4+ memory T cells with highest levels on EM T cells in HIV patients with mild or severe neurocognitive alterations. Interpretation The CD 4/ CD 8 ratio, the proportion of EM to naïve T cells and the immune activation profile of CD 4+ and CD 8+ T cells in PB and CSF might be useful parameters to monitor the efficacy of cART and to identify HIV patients at risk of further neurocognitive deterioration.