Identification of T lymphocytes in simian immunodeficiency virus encephalitis: distribution of CD8+ T cells in association with central nervous system vessels and virus.
T lymphocytes are found within brains infected with human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) where they are a minor, but consistently identified, population. However, little analysis of their phenotypes has been done, and questions concerning whether or not they are viral antigen specific has not been thoroughly examined. We investigated the central nervous system (CNS) of SIV-infected rhesus macaques to identify T-lymphocyte subsets in relation to virus-infected cells and brain microvessels. We have found that a sensitive antigen-retrieval technique greatly enhanced immunohistochemical detection of CD4+ and CD8+ T lymphocytes in control studies. In encephalitic brains of SIV-infected monkeys with acquired immunodeficiency syndrome (AIDS), we found a significant accumulation of CD8+ T lymphocytes but little-to-no accumulation of CD4+ T lymphocytes. CD4+ cells, when detected, were mostly monocyte/macrophages closely associated with CNS vessels. Using a combination of in situ hybridization for SIV RNA, and immunohistochemistry for CD8+ T lymphocytes and/or Glut-1 for endothelial cells on brain microvessels, we found CD8+ T lymphocytes with an angiocentric distribution often adjacent to virus-infected cells. In the CNS of animals with SIV encephalitis, there was a trend of CD8+ T lymphocytes that were not directly juxtaposed with CNS vessels. These data suggest that in brains of SIV-infected monkeys and HIV-infected humans, CD8+ T lymphocytes traffic to and are retained in the CNS in an angiocentric and possibly antigen-specific manner.
Kim
Woong-Ki
WK
Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
Corey
Sarah
S
Chesney
Gillian
G
Knight
Heather
H
Klumpp
Sherry
S
Wüthrich
Christian
C
Letvin
Norman
N
Koralnik
Igor
I
Lackner
Andrew
A
Veasey
Ronald
R
Williams
Kenneth
K
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002490:Central Nervous System / Q000821:virology*; D004195:Disease Models, Animal; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*