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Journal of Virology, November 2008, p. 10418-10428, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.01190-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Enhancement of Human Immunodeficiency Virus (HIV)-Specific CD8+ T Cells in Cerebrospinal Fluid Compared to Those in Blood among Antiretroviral Therapy-Naïve HIV-Positive Subjects{triangledown}

Shanmugalakshmi Sadagopal,1 Shelly L. Lorey,1 Louise Barnett,1 Rebecca Basham,1 Laurie Lebo,1 Husamettin Erdem,1 Kirsten Haman,3 Malcolm Avison,4,5 Kevin Waddell,4 David W. Haas,1,2 and Spyros A. Kalams1,2*

Departments of Medicine, Division of Infectious Diseases,1 Microbiology and Immunology,2 Psychiatry,3 Radiology and Radiological Sciences,4 Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 372325

Received 7 June 2008/ Accepted 8 August 2008

During untreated human immunodeficiency virus type 1 (HIV-1) infection, virus-specific CD8+ T cells partially control HIV replication in peripheral lymphoid tissues, but host mechanisms of HIV control in the central nervous system (CNS) are incompletely understood. We characterized HIV-specific CD8+ T cells in cerebrospinal fluid (CSF) and peripheral blood among seven HIV-positive antiretroviral therapy-naïve subjects. All had grossly normal brain magnetic resonance imaging and spectroscopy and normal neuropsychometric testing. Frequencies of epitope-specific CD8+ T cells by direct tetramer staining were on average 2.4-fold higher in CSF than in blood (P = 0.0004), while HIV RNA concentrations were lower. Cells from CSF were readily expanded ex vivo and responded to a broader range of HIV-specific human leukocyte antigen class I restricted optimal peptides than did expanded cells from blood. HIV-specific CD8+ T cells, in contrast to total CD8+ T cells, in CSF and blood were at comparable maturation states, as assessed by CD45RO and CCR7 staining. The strong relationship between higher T-cell frequencies and lower levels of viral antigen in CSF could be the result of increased migration to and/or preferential expansion of HIV-specific T cells within the CNS. This suggests an important role for HIV-specific CD8+ T cells in control of intrathecal viral replication.

* Corresponding author. Mailing address: Vanderbilt University Medical Center, MCN A2200, Nashville, TN 37232. Phone: (615) 322-2035. Fax: (615) 343-6160. E-mail: spyros.a.kalams{at}vanderbilt.edu

{triangledown} Published ahead of print on 20 August 2008.

Journal of Virology, November 2008, p. 10418-10428, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.01190-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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