title: Immune failure in the absence of profound CD4+ T-lymphocyte depletion in simian immunodeficiency virus-infected rapid progressor macaques.
abstract: 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.
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, Maryland 20852, USA. vhirsch@nih.gov
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Hirsch
authors.forename: Sampa
authors.initials: S
authors.lastname: Santra
authors.forename: Simoy
authors.initials: S
authors.lastname: Goldstein
authors.forename: Ronald
authors.initials: R
authors.lastname: Plishka
authors.forename: Alicia
authors.initials: A
authors.lastname: Buckler-White
authors.forename: Aruna
authors.initials: A
authors.lastname: Seth
authors.forename: Ilnour
authors.initials: I
authors.lastname: Ourmanov
authors.forename: Charles R
authors.initials: CR
authors.lastname: Brown
authors.forename: Ronald
authors.initials: R
authors.lastname: Engle
authors.forename: David
authors.initials: D
authors.lastname: Montefiori
authors.forename: Jennifer
authors.initials: J
authors.lastname: Glowczwskie
authors.forename: Kevin
authors.initials: K
authors.lastname: Kunstman
authors.forename: Steven
authors.initials: S
authors.lastname: Wolinsky
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
mesh_terms: 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
chemical_list: D000914:Antibodies, Viral; D013745:Tetanus Toxoid