HIV-1 gp120 induces IL-4 and IL-13 release from human Fc epsilon RI+ cells through interaction with the VH3 region of IgE.
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 alpha-chain of high-affinity receptor for IgE (Fc epsilon RI) 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 Fc epsilon RI+ cells.
Patella
V
V
University of Naples Federico II, Division of Clinical Immunology and Allergy, Naples, Italy.
Florio
G
G
Petraroli
A
A
Marone
G
G
D000328:Adult; D001491:Basophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000502:physiology*; D015497:HIV-1 / Q000145:classification / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007073:Immunoglobulin E / Q000378:metabolism*; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism*; D007075:Immunoglobulin M / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000378:metabolism*; D018793:Interleukin-13 / Q000378:metabolism*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007700:Kinetics; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009194:Myeloma Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology; D017455:Receptors, IgE / Q000096:biosynthesis*; D016559:Tacrolimus / Q000494:pharmacology
D015699:HIV Envelope Protein gp120; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D018793:Interleukin-13; D009194:Myeloma Proteins; D010446:Peptide Fragments; D017455:Receptors, IgE; D015847:Interleukin-4; D007073:Immunoglobulin E; D016572:Cyclosporine; D016559:Tacrolimus