Immune failure in the absence of profound CD4+ T-lymphocyte depletion in simian immunodeficiency virus-infected rapid progressor macaques.
A fraction of simian immunodeficiency virus (SIV)-infected macaques develop rapidly progressive disease in the apparent absence of detectable SIV-specific antibody responses. To characterize the immunopathogenesis of this syndrome, we studied viral load, CD4+ T-lymphocyte numbers as well as cellular and humoral immune responses to SIV and other exogenous antigens in four SIVsm-infected rhesus macaques that progressed to AIDS 9 to 16 weeks postinoculation. Each of these animals exhibited high levels of viremia but showed relatively preserved CD4 T lymphocytes in blood and lymphoid tissues at the time of death. Transient SIV-specific antibody responses and cytotoxic T-lymphocyte responses were observed at 2 to 4 weeks postinoculation. Two of the macaques that were immunized sequentially with tetanus toxoid and hepatitis A virus failed to develop antibody to either antigen. These studies show that the SIV-infected rapid progressor macaques initially mounted an appropriate but transient cellular and humoral immune response. The subsequent immune defect in these animals appeared to be global, affecting both cellular and humoral immunity to SIV as well as immune responses against unrelated antigens. The lack of CD4 depletion and loss of humoral and cellular immune responses suggest that their immune defect may be due to an early loss in T helper function.
Hirsch
Vanessa M
VM
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, Maryland 20852, USA. vhirsch@nih.gov
Santra
Sampa
S
Goldstein
Simoy
S
Plishka
Ronald
R
Buckler-White
Alicia
A
Seth
Aruna
A
Ourmanov
Ilnour
I
Brown
Charles R
CR
Engle
Ronald
R
Montefiori
David
D
Glowczwskie
Jennifer
J
Kunstman
Kevin
K
Wolinsky
Steven
S
Letvin
Norman L
NL
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D018450:Disease Progression; D030041:Hepatitis A virus / Q000276:immunology; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000503:physiopathology*; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D013997:Time Factors; D019562:Viral Load; D014774:Virulence
D000914:Antibodies, Viral; D013745:Tetanus Toxoid