Krauss S, Kufer P, Federle C, Riethmuller G, Rieber EP; International Conference on AIDS.

Int Conf AIDS. 1991 Jun 16-21; 7: 76 (abstract no. TU.A.76).

Institute for Immunology, University of Munich, Munich, FRG

OBJECTIVE: Basophils and mast cells are the main effector cells in type I hypersensitivity and are potent stimulators of inflammatory reactions. Recently mouse mast cells have been implicated in cytotoxic reactions and human virus specific IgE has been demonstrated. Therefore, we wondered whether basophils and mast cells could be engaged into the elimination of HIV infected cells. In a first approach we evaluated the cytotoxic capacity of human basophils and designed tools to target basophils to HIV infected cells. METHODS: Basophils from healthy blood donors were obtained at greater than 96% purity by density centrifugation, followed by negative selection using monoclonal CD2 and CD14 antibodies and final purification by anti-IgE rosetting. In order to bring basophils into contact with HIV or HIV-infected cells a recombinant IgE/CD4-hybrid molecule was constructed where the VH domain of IgE was replaced by the gp120-binding first and second domain of the CD4 molecule. RESULTS: Stimulation of basophils with anti-IgE led to release of histamine and TNF alpha. TNF alpha mRNA was demonstrated in purified basophils. Release of mediators could be enhanced by IL-3. The IgE/CD4-construct was able to bind both the Fcepsilon receptor I on basophils and the low affinity Fcepsilon receptor II (CD23) on lymphoblastoid B cell lines. It was also capable to block gp120 binding to CD4+ cells. When armed with the IgE/CD4-construct basophils could be induced to release histamine by monoclonal CD4 antibody as well as by free HIV and HIV infected H9 cells. CONCLUSION: Our work provides evidence that human basophils have cytotoxic capacity and can be specifically directed against HIV infected cells. Thus, recruitment of the potent IgE-dependent effector system may supplement therapeutic strategies against HIV infection.

Publication Types:

• Meeting Abstracts

Keywords:

• AIDS Vaccines
• Acquired Immunodeficiency Syndrome
• Animals
• Antibodies, Anti-Idiotypic
• Antigens, CD4
• Basophils
• HIV
• HIV Antigens
• HIV Envelope Protein gp120
• HIV Infections
• HIV Seropositivity
• Humans
• Hypersensitivity, Immediate
• Lymphocytes
• Mast Cells
• Mice
• Receptors, IgE
• anti-IgE
• immunology

Other ID:

• 2007691

UI: 102184711

From Meeting Abstracts