Loss of Naive Cells Accompanies Memory CD4 super(+) T-Cell Depletion during Long-Term Progression to AIDS in Simian Immunodeficiency Virus-Infected Macaques

• Published in: Journal of virology Vol. 81; no. 2; pp. 893 - 902
• Main Authors: Nishimura, Yoshiaki, Igarashi, Tatsuhiko, Buckler-White, Alicia, Buckler, Charles, Imamichi, Hiromi, Goeken, Robert M, Lee, Wendy R, Lafont, Bernard AP, Byrum, Russ, Lane, HClifford, Hirsch, Vanessa M, Martin, Malcolm A
• Format: Journal Article
• Language: English
• Published: 01.01.2007
• Subjects: Human immunodeficiency virus; Macaca mulatta; Simian immunodeficiency virus
• ISSN: 0022-538X; 1098-5514

Human immunodeficiency virus and simian immunodeficiency virus (SIV) induce a slow progressive disease, characterized by the massive loss of memory CD4 super(+) T cells during the acute infection followed by a recovery phase in which virus replication is partially controlled. However, because the initial injury is so severe and virus production persists, the immune system eventually collapses and a symptomatic fatal disease invariably occurs. We have assessed CD4 super(+) T-cell dynamics and disease progression in 12 SIV-infected rhesus monkeys for nearly 2 years. Three macaques exhibiting a rapid progressor phenotype experienced rapid and irreversible loss of memory, but not naive, CD4 super(+) T lymphocytes from peripheral blood and secondary lymphoid tissues and died within the first 6 months of virus inoculation. In contrast, SIV-infected conventional progressor animals sustained marked but incomplete depletions of memory CD4 super(+) T cells and continuous activation/proliferation of this T-lymphocyte subset. This was associated with a profound loss of naive CD4 super(+) T cells from peripheral blood and secondary lymphoid tissues, which declined at rates that correlated with disease progression. These data suggest that the persistent loss of memory CD4 super(+)T cells, which are being eliminated by direct virus killing and activation-induced cell death, requires the continuous differentiation of naive into memory CD4 super(+) T cells. This unrelenting replenishment process eventually leads to the exhaustion of the naive CD4 super(+)T-cell pool and the development of disease.