Mechanisms of IgE elevation in HIV-1 infection.
Serum IgE levels are high in adults and children with HIV-1 infection and could be a marker of poor prognosis. Allergic reactions and adverse reactions to drugs also tend to increase in HIV-1-infected individuals. An imbalance between a "T(H)1-like" and a "T(H)2-like" cytokine profile has been documented in HIV-1 infection. We have demonstrated that HIV-1 gp 120 from different clades is a stimulus for histamine and cytokine (IL-4 and IL-13) release from basophils. Gp 120 acts as a viral superantigen, interacting with the V(H)3 region of IgE to induce mediator release from human Fc epsilonRI+ cells. Human basophils and mast cells express the chemokine receptor CCR3, which binds the chemokines eotaxin and RANTES. By interacting with the CCR3 receptor on Fc epsilonRI+ cells, HIV-I Tat protein is a potent chemoattractant for human basophils and lung mast cells. Preincubation of basophils with Tat protein upregulates mRNA CCR3 and the surface expression of this chemokine receptor. Tat also induces IL-4 and IL-13 release from basophils. Extracellular Tat can influence the directional migration of human Fc epsilonRI+ cells, the expression of chemokine receptor CCR3, and the release of T(H)2 cytokines. Our results indicate two novel mechanisms by which two HIV-1 proteins, gp120 and Tat, trigger the release of cytokines critical for T(H)2 polarization from human Fc epsilonRI+ cells.
Marone
G
G
Division of Clinical Immunology and Allergy, University of Naples Federico II, Italy.
Florio
G
G
Triggiani
M
M
Petraroli
A
A
de Paulis
A
A
D015696:Gene Products, tat / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D018448:Models, Immunological; D017455:Receptors, IgE; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D015699:HIV Envelope Protein gp120; D017455:Receptors, IgE; D054322:tat Gene Products, Human Immunodeficiency Virus; D007073:Immunoglobulin E