CD4 deficits and disease course acceleration can be driven by a collapse of the CD8 response in rhesus macaques infected with simian immunodeficiency virus.
OBJECTIVE
Defects in memory CD4+ T cells correlate with development of AIDS in monkeys infected with simian immunodeficiency virus, but the early events leading to these deficits are unknown. We explored the role of cells specific to simian immunodeficiency virus and CD8 cells in the determination of CD4 failure and rapid disease course.


METHODS
Using MamuA*01-restricted Gag and Tat epitope tetramers, we compared the kinetics of specific response in animals with regular (REG) and rapid (RAP) progression. Expressions of memory, activation and proliferation markers were examined on the global CD8 pool, as well as on CD4 T cells in those animals. In-vivo CD8 depletion in non-MamuA*01 animals was used to investigate CD8 collapse as an event leading to disease progression and CD4 deficits.


RESULTS
In animals with a rapid disease course, an initial development of cytotoxic T lymphocytes specific to simian immunodeficiency virus is followed by collapse accompanied by global changes in CD8 cells and occurs in synchrony with the characteristic CD4 deficiencies. Antibody-mediated depletion of CD8 cells early after infection with simian immunodeficiency virus induces similar changes in the CD4 cells and rapid development of AIDS.


CONCLUSIONS
CD8 collapse at acute time points may result in uncontrolled viral load and development of a defective and insufficient CD4 population. Our results indicate that early breakdown in CD8 cells leads to CD4 deficits and rapid progression to AIDS and suggest that therapeutic approaches should aim at strengthening CD8 T cells early after viral infection.
Marcondes
Maria Cecilia G
MC
The Scripps Research Institute, Molecular and Integrative Neurosciences Department, La Jolla, California, USA.
Sopper
Sieghart
S
Sauermann
Ulrike
U
Burdo
Tricia H
TH
Watry
Debbie
D
Zandonatti
Michelle
M
Fox
Howard S
HS
D000818:Animals; D001921:Brain / Q000276:immunology / Q000821:virology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D018450:Disease Progression; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019562:Viral Load