IgE anti-HIV-1 in serum of HIV-1 infected children inhibits HIV-1 production in vitro and IgE mediates cytotoxicity against lymphoma cells expressing HIV-1 and peripheral blood mononuclear cells from an HIV-1 seropositive patien

The role of IgE antibodies in the long term survival of certain HIV-1 seropositive children was investigated. These children had acquired HIV-1 through maternal transmission, are now 8--12 years old, in relatively good health, with no opportunistic infections, despite reduced numbers of blood CD4+ T cells. The ability of serum from these children, which contained IgE anti-HIV-1 antibodies (Western blot), to regulate HIV-1 (p24 core antigen) production by cultured peripheral blood mononuclear cells (PBMC) which were (a) previously infected with HIV-1 in vitro with a T cell tropic clone of HIV-1, or (b) co-cultured with PBMC from an HIV-1 seropositive donor (primary HIV-1). was investigated. Serum from all children in strongly suppressed (>90%) p24 antigen production, effects which were reversed if serum was first depleted of IgE (immunoaffinity column). In contrast, removal of IgG (protein G sepharose) had no effect.;The ability of serum from these children, which contained ISE anti-HIV-1 antibodies, to mediate cytotoxicity (lactate dehydrogenase release) when cultured for 4 hr at 37°C with (a) TF228.1.16 lymphoma cells bearing HIV-1 proteins gp160, gp120, and gp41 (target cells) and PBMC from an HIV-1 seronegative donor (effector cells), or (b) PBMC from an HIV-1 seropositive donor, was investigated. Cytotoxicity was observed whenever the target cells were cultured with serum, either in the presence or absence of effector cells (9.1--26.3%). Even greater cytotoxicity was observed when these sera were cultured with PBMC from an HIV-1 seropositive donor (62--94%). In contrast, cytotoxicity was reduced or abrogated if the serum used was depleted of IgE prior to culture. No cytotoxicity was observed using serum from an HIV-1 seronegative donor containing ragweed specific IgE. When purified IgE containing IgE anti-HIV-1 antibodies was included in cultures with target and effector cells, cytotoxicity also was observed (10%); no cytotoxicity was observed with target cells alone. Further, when PBMC from an HIV-1 seropositive donor were cultured with IgE which had been purified from either (a) serum containing IgE anti-HIV-1 antibodies, or (b) serum from an HIV-1 seropositive child which did not contain IgE anti-HIV-1 antibodies, even higher levels of cytotoxicity were observed (36--47%). This suggests that IgE may recognize both HIV-1 and non-HIV-1 antigens an cell surface. In contrast, IgE purified from serum of HIV-1 seropositive children never mediated cytotoxicity against PBMC from an HIV-1 seronegative donor, and no cytotoxicity was observed when IgE purified from serum of an HIV-1 seronegative donor containing ragweed specific IgE was cultured with PBMC from either HIV-1 seropositive or HIV-1 seronegative donors. IgE mediated suppression of HIV-1 p24 core antigen production, as well as IgE dependent cytotoxicity, were both reversed when serum samples were heated to 56°C for 1 hr, a procedure which inhibits cytophilic binding of IgE to leukocytes, but which does not affect other immunoglobulin isotypes. Suppression of cytotoxicity could not be restored when serum from an HIV-1 seronegative donor was added as a source of complement. These findings suggest that IgE antibodies may contribute to the lack of disease progression observed in virtually all children who produced IgE in our studies by inhibiting virus production and facilitating the destruction of infected cells.