HIV Type 1-Specific IgE in Serum of Long-Term Surviving Children Inhibits HIV Type 1 Productionin Vitro

Abstract

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.

IgE, CD8+CD60+ T Cells and IFN-α in Human Immunity to Parvovirus B19 in Selective IgA Deficiency

“…Similar studies in our laboratory [3] in HIV-1 disease have revealed a persistence of HIV-1-specific IgE after 210 days, and retained its ability to suppress HIV-1 production in vitro [3]. Further, we have demonstrated that specific IgE anti-HIV-1 antibodies may protect against HIV-1 disease progression by promoting cytotoxic responses or by suppressing virus production [2][3][4]. Thus, the association of IgE with viral infection and immunity could be consistent with an important immune function of IgE.…”

“…The fact that this study demonstrates the presence and persistence of IgE anti-parvovirus B19 antibodies as late as 3 years after presentation of symptoms and in both healthy and immunodeficient patients elucidates a unique characteristic of IgE biology. Similar studies in our laboratory [3] in HIV-1 disease have revealed a persistence of HIV-1-specific IgE after 210 days, and retained its ability to suppress HIV-1 production in vitro [3]. Further, we have demonstrated that specific IgE anti-HIV-1 antibodies may protect against HIV-1 disease progression by promoting cytotoxic responses or by suppressing virus production [2][3][4].…”

“…IgE anti-human immunodeficiency virus type 1 (HIV-1) [2][3][4], parvovirus B19 [5], parainfluenza [6], and respiratory syncytial virus [7,8] have been described. Studies in our laboratory were the first to describe a functional role for IgE anti-HIV-1 in that IgE anti HIV-1 antibodies strongly suppress virus replication in vitro [3], and possibly may contribute to nonprogressor status. In these studies, an IgE mediating cytotoxicity mechanism may be responsible for suppression of HIV-1 [3,4].…”

Impact of Selenium Supplementation in Neutropenia and Immunoglobulin Production in Childhood Cancer Patients

“…In fact, in previously conducted researches, the authors noted that IgE has antiviral action, acting effectively. 55 Similarly, in two of his studies, Karagiannis et al showed that IgE antibodies are able to increase the survival of animals bearing ovarian carcinoma through the ADCC mechanism against tumor cells. 56,57 In our study, we did not assess the specificity of IgE antibodies, and thus, it is not possible to associate the production of this antibody to protection mechanisms against tumor cells in the patients studied.…”

IgE anti-respiratory syncytial virus antibodies detected in serum of pediatric patients with asthma

“…Previous studies in our laboratory demonstrated that IgE may play an important role in immunity to specific viruses including Parvovirus B19 [30], Varicella Zoster Virus [31,32], Influenza Virus [33] and HIV-1 [34,35] In addition, earlier studies in our laboratory found that serum from certain HIV-1 infected pediatric long-term survivors contain agents that inhibit HIV-1 production in vitro, including anti-HIV-1 IgE [34]; it has been suggested that cytotoxicity plays a role in anti-HIV-1 IgE-mediated inhibition of virus production [35] Thus, these specific IgE responses may play an important role in viral memory responses, and provide protection against viral infection.…”