Enrichment and persistence of virus-specific CTL in the brain of simian immunodeficiency virus-infected monkeys is associated with a unique cytokine environment.
The host reaction to infection of the brain contributes to a number of CNS pathologies including neuro-AIDS. In this study, we have identified the accumulation of SIV-specific CTL in the brains of SIV-infected animals who have neurophysiological abnormalities but are otherwise asymptomatic. SIV-specific CTL enter the brain early after viral infection and are maintained in the brain even when those reactive with an immunodominant epitope in Tat are lost from the rest of the body. The specialized CNS environment contributes to this unique outcome. Following SIV infection, brain levels of IL-15 were significantly elevated whereas IL-2 was absent, creating an environment that favors CTL persistence. Furthermore, in response to IL-15, brain-derived CD8(+) T cells could expand in greater numbers than those from spleen. The accumulation, persistence, and maintenance of CTL in the brain are closely linked to the increased levels of IL-15 in the absence of IL-2 in the CNS following SIV infection.
Marcondes
Maria Cecilia G
MC
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. cmarcond@scripps.edu
Burdo
Tricia H
TH
Sopper
Sieghart
S
Huitron-Resendiz
Salvador
S
Lanigan
Caroline
C
Watry
Debbie
D
Flynn
Claudia
C
Zandonatti
Michelle
M
Fox
Howard S
HS
D000595:Amino Acid Sequence; D000818:Animals; D001769:Blood / Q000276:immunology; D001921:Brain / Q000276:immunology*; D002470:Cell Survival; D002555:Cerebrospinal Fluid / Q000276:immunology; D016207:Cytokines / Q000032:analysis / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D019409:Interleukin-15 / Q000032:analysis / Q000276:immunology*; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D019409:Interleukin-15