CD8+ cell depletion amplifies the acute retroviral syndrome.
The duration and severity of the symptomatology present during the early phase of human immunodeficiency virus (HIV) infection (known as the acute retroviral syndrome) is associated with alterations in the clinical profile of infection, such as a shortening of duration between infection with HIV and the onset of neurocognitive impairment and acquired immunodeficiency syndrome (AIDS). Viral-specific CD8+ cytotoxic T lymphocytes (CTLs) and CD8+ natural killer (NK) cells play a key role in antiviral immunity. Loss of CD8+ cells or their functional impairment during the early period of infection is associated with a rapid progression to AIDS in nonhuman primate studies. However, no studies have determined whether CD8+ cell loss or impairment is associated with symptoms of acute retroviral illness such as fever. In this study, the authors compared the early phase of simian immunodeficiency virus (SIV) infection in animals that were treated with the anti-CD8 monoclonal antibody cM-T807 to deplete CD8+ cells during the early period of infection (SIV+ CD8- group) to those with intact CD8+ cells (SIV+ CD8+ group). The SIV+ CD8- group had an enhanced acute retroviral syndrome when compared to the SIV+ CD8+ group. The SIV+ CD8- group also had prolonged high viral loads and distinct alterations in the proinflammatory cytokines interleukin (IL)-6 and interferon (IFN)-alpha, as well as in monocyte chemoattractant protein (MCP)-1. CD8+ cell depletion, therefore, appears to enhance symptoms of the acute retroviral syndrome and alters several of the immunological factors associated with the early phase of infection.
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA. madden@scripps.edu
Lisa J
LJ
Madden
Michelle A
MA
Zandonatti
Claudia T
CT
Flynn
Mike A
MA
Taffe
M Cecilia G
MC
Marcondes
Jörn E
JE
Schmitz
Keith A
KA
Reimann
Steven J
SJ
Henriksen
Howard S
HS
Fox
D000208:Acute Disease; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000821:virology*; D018932:Chemokine CCL2 / Q000097:blood; D005334:Fever / Q000276:immunology / Q000401:mortality / Q000821:virology; D016898:Interferon-alpha / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008253:Macaca mulatta; D008297:Male; D009043:Motor Activity; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology*; D016019:Survival Analysis; D019562:Viral Load
D018932:Chemokine CCL2; D016898:Interferon-alpha; D015850:Interleukin-6