HIV-1 gp120 Induces IL-4 and IL-13 Release from Human FcεRI+ Cells Through Interaction with the VH3 Region of IgE

Abstract

HIV-1 glycoprotein (gp) 120 from different clades is a potent stimulus for IL-4 and IL-13 release from basophils purified from healthy individuals seronegative for Abs to HIV-1 and HIV-2. IL-4 mRNA, constitutively present in basophils, was increased after stimulation by gp120 and was inhibited cyclosporin A and tacrolimus. IL-4 and IL-13 secretion from basophils activated by gp120 was not correlated. There was a correlation between the maximum gp120- and anti-IgE-induced IL-4 release from basophils. The average t1/2 gp120-induced IL-4 release was lower than for IL-13 release. Basophils from which IgE had been dissociated by brief exposure to lactic acid no longer released IL-4 in response to gp120 or to anti-IgE. The response to a mAb cross-linking the α-chain of high-affinity receptor for IgE (FcεRI) was unaffected by this treatment. Three human VH3+ monoclonal IgM inhibited gp120-induced secretion of IL-4 from basophils. In contrast, VH6+ monoclonal IgM did not inhibit the release of IL-4 induced by gp120. Synthetic peptides distant from the NH2 and COOH termini of gp120MN inhibited the activating property of gp120MN. These results indicate that gp120, which acts as a viral superantigen, interacts with the VH3 region of IgE to induce the release of IL-4 and IL-13 from human FcεRI+ cells.

Tat Protein Is an HIV-1-Encoded β-Chemokine Homolog That Promotes Migration and Up-Regulates CCR3 Expression on Human FcεRI+ Cells

“…Second, the chemotactic activity of Tat on human Fc⑀RI ϩ cells might contribute to increase the local density of mast cells and basophils available for HIV-1 interaction through the virus bound or shed gp120. In fact, we have recently demonstrated that gp120 from different clades interacts with the V H 3 region of IgE present on human Fc⑀RI ϩ (35). Third, the superantigenic interaction between gp120 and IgE leads to the rapid synthesis and release of IL-4 and IL-13 from human Fc⑀RI ϩ cells (35).…”

“…We have recently demonstrated that the interaction between a gp120 binding site and the V H 3 domain of IgE on human basophils and mast cells induces the release of Th2 cytokines (IL-4 and IL-13) from human Fc⑀RI ϩ cells without synthesizing Th1-type cytokines (e.g., IFN-␥) (35). The presence of CCR3 receptors on the majority of basophils (39,40) and on a significant percentage of human mast cells (38,40) and their role as coreceptor for HIV-1 infection (7)(8)(9)(10) suggest that the interplay between Tat protein, which upregulates CCR3 receptors, and Fc⑀RI ϩ cells could facilitate HIV infection of these cells.…”

“…Basophils (ϳ6 ϫ 10 4 basophils/tube) or mast cells (ϳ3 ϫ 10 4 cells/tube) were resuspended in PCG, and 0.1 ml of the cell suspension was placed in 12 ϫ 75-mm polyethylene tubes (Sarstadt, Princeton NJ) and warmed to 37°C; 0.1 ml of each prewarmed releasing stimulus was added, and incubation was continued at 37°C for 45 min (35). At the end of this step, the reaction was stopped by centrifugation (1000 ϫ g, 22°C, 2 min), and the cell-free supernatants were stored at Ϫ20°C for subsequent assay of histamine content with an automated fluorometric technique (48).…”

“…Similarly, immunologic activation of mast cells leads to the synthesis of IL-4 and IL-13 (31)(32)(33)(34). We have recently demonstrated that HIV-1 gp120 from different clades is a potent stimulus for IL-4 and IL-13 release from basophils from healthy individuals seronegative for Abs to HIV-1 and HIV-2 (35). Because HIV-1 enters the body predominantly through mucosal surfaces and because the early phases of infection are associated with high levels of viremia (1,36), mast cells and basophils can be exposed to shed or virusbound gp120.…”

A Crystallin Fold in the Interleukin-4-inducing Principle of Schistosoma mansoni Eggs (IPSE/α-1) Mediates IgE Binding for Antigen-independent Basophil Activation

“…Basophil activation by IPSE/␣-1 was found to depend on the presence of IgE on the surface of the basophils irrespective of IgE's antigen specificity (7,12). IgE-dependent, antigen-independent basophil activation is well known from multivalent lectins or B cell superantigens, which cross-link IgE via binding to its carbohydrate side chains or directly to its immunoglobulin backbone, respectively (13,14). However, molecular details of the mechanism of action of IPSE/␣-1 are not yet known.…”