Polyspecific self-reactive antibodies in individuals infected with human immunodeficiency virus facilitate T cell deletion and inhibit costimulatory accessory cell function.
Self-reactive polyspecific IgG antibodies (PSAs) arise in human immunodeficiency virus (HIV)-seropositive subjects before they develop AIDS. Self-reactive PSA levels correlate with the destruction of CD8 T cells in HIV-infected individuals and mediate the antibody-dependent cellular toxicity-based destruction of human T cells in tissue culture. PSAs react across the species barrier and bind to T cell antigens in mice. Such reactivity with mouse lymphocytes was not detected in normal human serum. Injection of human PSA IgG causes massive T cell depletion in the spleen, lymph nodes, and thymus in mice: evidence that PSA IgG facilitates T cell destruction in vivo. In addition to facilitating macrophage cytotoxicity, self-reactive PSA IgG inhibits the macrophage-mediated activation of T cells with antigen receptor-specific monoclonal antibody or with antigen. Exogenous costimulatory stimuli or interleukin (IL)-12 can reverse the inhibition. In contrast, exogenous IL-10 mimics this inhibition. These data implicate PSA IgG as a pathogenic factor in the development of HIV disease.
Wang
Z q
Zq
Departments of Microbiology, Immunology, New York Medical College, New York, USA.
Horowitz
H W
HW
Orlikowsky
T
T
Hahn
B I
BI
Trejo
V
V
Bapat
A S
AS
Mittler
R S
RS
Rayanade
R J
RJ
Yang
S Y
SY
Hoffmann
M K
MK
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D018023:HIV Seronegativity / Q000276:immunology; D006679:HIV Seropositivity / Q000097:blood / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000097:blood*; D018664:Interleukin-12 / Q000494:pharmacology; D008231:Lymphopenia / Q000097:blood / Q000209:etiology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012016:Reference Values
D001323:Autoantibodies; D007074:Immunoglobulin G; D011948:Receptors, Antigen, T-Cell; D018664:Interleukin-12