Related Experiment Videos
Intercellular adhesion molecules (ICAM)-1 ICAM-2 and ICAM-3 function as counter-receptors for lymphocyte
L Butini1, A R De Fougerolles, M Vaccarezza
1Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Insights
Lymphocyte function-associated molecule 1 (LFA-1) drives HIV syncytia. Blocking intercellular adhesion molecules (ICAM-1, ICAM-2, ICAM-3) simultaneously with antibodies fully inhibited this process, highlighting their critical role.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Lymphocyte function-associated molecule 1 (LFA-1) is crucial for human immunodeficiency virus (HIV)-mediated syncytia formation.
- The specific roles of intercellular adhesion molecules (ICAMs) in this process require further elucidation.
Purpose of the Study:
- To investigate the involvement of ICAM-1, ICAM-2, and ICAM-3 in HIV-induced syncytia formation.
- To determine if blocking ICAMs can inhibit syncytia formation mediated by LFA-1.
Main Methods:
- Analyzing the effect of monoclonal antibodies (mAbs) against ICAM-1, ICAM-2, and ICAM-3 on syncytia formation.
- Utilizing phytohemagglutinin (PHA)-activated lymphocytes infected with HIV strains in vitro.
- Employing co-culture systems with HIV envelope-expressing T cell lines and PHA-activated lymphocytes.
Main Results:
- Complete inhibition of syncytia formation was achieved only when mAbs against all three ICAMs (ICAM-1, ICAM-2, ICAM-3) were added simultaneously.
- Individual or dual antibody additions did not result in complete blockage, suggesting a cooperative mechanism.
Conclusions:
- The interaction between LFA-1 and ICAMs is a critical step in HIV-mediated syncytia formation.
- ICAM-1, ICAM-2, and ICAM-3 act as essential receptor molecules for LFA-1-dependent syncytia formation during HIV infection.
Abstract:
It has been previously demonstrated that lymphocyte function-associated molecule 1 (LFA-1) plays a major role in human immunodeficiency virus (HIV)-mediated syncytia formation. In the present study we investigated the involvement of intercellular adhesion molecule-1 (ICAM-1), ICAM-2 and ICAM-3 in the process. The ability of monoclonal antibodies (mAb) directed against ICAM-1, ICAM-2 and ICAM-3 to block syncytia was analyzed either in phytohemagglutinin (PHA)-activated lymphocytes infected in vitro with primary or laboratory strains of HIV or by coculturing a T cell line stably expressing HIV envelope with PHA-activated lymphocytes. Complete inhibition of syncytia formation was observed only by the simultaneous addition to the cell cultures of all (i.e. anti-ICAM-1, anti-ICAM-2 and anti-ICAM-3) mAb. These results indicate that the interaction between LFA-1 and ICAM is a critical step in HIV-mediated syncytia formation, and that ICAM-1, ICAM-2 and ICAM-3 are the receptor molecules for the LFA-1-dependent syncytia formation.