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High Frequency of Virus-Specific CD8⁺ T Cells in the Central Nervous System of Macaques Chronically Infected with Simian Immunodeficiency Virus SIVmac251

Marcin Moniuszko,¹ Charlie Brown,² Ranajit Pal,³ Elzbieta Tryniszewska ,^1, Wen-Po Tsai,¹ Vanessa M. Hirsch,² and Genoveffa Franchini^1*

Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, Maryland 20892-5055,¹ Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Disease, Rockville, Maryland 20852,² and Advanced BioScience Laboratories, Inc., Kensington, Maryland 20895³

Received 24 March 2003/ Accepted 7 August 2003

Infection with human immunodeficiency virus or simian immunodeficiency virus (SIV) induces virus-specific CD8⁺ T cells that traffic to lymphoid and nonlymphoid tissues. In this study, we used Gag-specific tetramer staining to investigate the frequency of CD8⁺ T cells in peripheral blood and the central nervous system of Mamu-A*01-positive SIV-infected rhesus macaques. Most of these infected macaques were vaccinated prior to SIVmac251 exposure. The frequency of Gag_181-189 CM9 tetramer-positive cells was consistently higher in the cerebrospinal fluid and the brain than in the blood of all animals studied and did not correlate with either plasma viremia or CD4⁺-T-cell level. Little or no infection in the brain was documented for most animals by nucleic acid sequence-based amplification or in situ hybridization. These data suggest that this Gag-specific response may contribute to the containment of viral replication in this locale.

Present address: Third Department of Pediatrics, Medical Academy of Bialystok, Waszyngtona 17, Poland.

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