140. Does migration of immune cells into the CNS play a role in HIV-associated neurocognitive impairment during antiretroviral therapy?

• Published in: Brain, behavior, and immunity behavior, and immunity, 2013-09, Vol.32, p.e40-e41
• Main Authors: Hong, S, Schrier, R.D, Kao, Y, Vaida, F, Cherner, M, Crescini, M, Ellis, R, Letendre, S
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Psychiatry
• ISSN: 0889-1591; 1090-2139
• DOI: 10.1016/j.bbi.2013.07.152

A substantial proportion of HIV + individuals suffer from HIV-associated neurocognitive impairment (NCI). Likely pathogenic mechanisms include neurotoxicity from persistent immune activation during suppressive antiretroviral therapy (ART). The investigation of activated, CNS-invading leukocytes in relation to HIV-associated NCI is in its infancy. We investigated lymphocyte migration into the CNS in 30 HIV + individuals with ( N = 14) and without NCI who participated in a CNS-penetrating antiretroviral therapy trial. Differentiation status of CD4 and CD8 memory T-cells (central memory, CM; effector memory, EM; CD45RA + EM, EMRA) and expression of chemokine receptor CXCR3 and integrin CD49d in peripheral blood and cerebrospinal fluid (CSF) were compared using flow cytometry. NCI was defined by a global deficit score (GDS) ⩾0.5 obtained from a comprehensive neuropsychological test battery. At baseline, greater proportions of highly differentiated and migration-marker-expressing memory T-cells were found in CSF compared to blood: higher %EM in CSF for CD4 and CD8 cells. Also, CSF-derived CD4 memory T-cells expressed greater levels of CXCR3 and CD49d ( p ’s < .05 to.001). NCI was associated with higher %CXCR3 + CD4 EM in CSF ( p < .10). Baseline to 16-week post-ART initiation/change ( N = 16), %CD49d + CD4 EM changes in blood predicted the changes in GDS over time ( p < .10). Our findings provide evidence suggesting migration of highly differentiated and activated T cells into the CNS in HIV and its implications in NCI during suppressive ART.