HIV type 1-specific IgE in serum of long-term surviving children inhibits HIV type 1 production in vitro.
We previously identified a group of long-term pediatric survivors who had acquired HIV-1 through maternal transmission; had not received antiretroviral therapy; are now >8 years old, in good health, and with no opportunistic infections; and have not failed to thrive, although they have greatly decreased numbers of blood CD4+ T cells (<500/mm(3)). All the children have elevated total serum IgE levels (210-2475 IU/ml) and make anti-HIV-1 IgE or IgE directed against non-HIV-1 specificities (radioimmunoassay, Western blot assay); they have no detectable antigenemia. We have now studied the ability of anti-HIV-1 IgE in serum obtained from these children to regulate (1) production of HIV-1 by interleukin 2/phytohemagglutinin (IL-2/PHA)-stimulated peripheral blood mononuclear cells (PBMCs) taken from HIV-1-seronegative donors and infected with a T cell-tropic clone of HIV-1, and (2) transmission of a primary HIV-1 strain from adult AIDS patients to uninfected IL-2/PHA-stimulated PBMCs (p24 core antigen production). High levels of HIV-1 production were observed when PBMCs were cultured for 5 days in the presence of HIV-1-seronegative donor serum that was either IgE positive or IgE negative (IgE, >100 or <100 IU/ml, respectively). HIV-1 production also was observed when PBMCs were cultured with HIV-1-infected donor serum that either contained IgE directed against non-HIV-1 specificities or was IgE negative; these levels were 40% less than those seen with sera from the HIV-1-seronegative donors. Far greater inhibition of virus production was observed if the serum in culture contained anti-HIV-1 IgE (>95%). Virus neutralization did not appear to account for the inhibition obtained with anti-HIV-1 IgE-containing serum because virus production was not suppressed in cultures to which serum was added immediately preinfection (<10%), but was strongly suppressed when serum was added 1.5 hr postinfection (>95%). The inhibition of virus production obtained with serum containing anti-HIV-1 IgE was reversed when (1) serum was depleted of IgE (immunoaffinity), but not when it was depleted of IgG (protein G-Sepharose) before inclusion in culture postinfection, (2) anti-IgE, but not anti-IgG, was included in culture, or (3) serum was heat treated before culture. The results indicate that serum from certain HIV-1-infected pediatric long-term survivors contains agents that inhibit HIV-1 production in vitro, and that these agents include anti-HIV-1 IgE. They suggest that a cytotoxic event, rather than virus neutralization, plays an important role in anti-HIV-1 IgE-mediated inhibition of virus production.
Pellegrino
Michael G
MG
Department of Pathology, State University of New York Downstate Medical Center, Brooklyn, New York 11203, USA.
Bluth
Martin H
MH
Smith-Norowitz
Tamar
T
Fikrig
Senih
S
Volsky
David J
DJ
Moallem
Hamid
H
Auci
Dominick L
DL
Nowakowski
Maja
M
Durkin
Helen G
HG
D018791:CD4 Lymphocyte Count; D002478:Cells, Cultured; D002648:Child; D005260:Female; D015483:HIV Antibodies / Q000097:blood / Q000494:pharmacology*; D016655:HIV Core Protein p24; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood* / Q000494:pharmacology; D018445:Infectious Disease Transmission, Vertical; D007963:Leukocytes, Mononuclear / Q000821:virology; D008213:Lymphocyte Activation; D008297:Male; D013601:T-Lymphocytes / Q000821:virology; D014779:Virus Replication
D015483:HIV Antibodies; D016655:HIV Core Protein p24; D007073:Immunoglobulin E