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CD43 interferes with T-lymphocyte adhesion
B Ardman1, M A Sikorski, D E Staunton
1Department of Medicine, New England Medical Center Hospitals, Boston, MA 02111.
Insights
CD43, a cell surface protein, hinders T-cell adhesion to other cells by interfering with leukocyte function-associated antigen 1 binding. This suggests CD43 regulates T-cell interactions and immune responses.
Area of Science:
- Immunology
- Cell Biology
Background:
- CD43 is a cell-surface sialoglycoprotein found on most leukocytes.
- Its precise physiological role in cell adhesion remains unclear.
Purpose of the Study:
- To investigate the role of CD43 in intercellular adhesion.
- To determine if CD43 influences T-lymphocyte binding to other cells.
Main Methods:
- Compared human T-lymphocyte adherence to HeLa cells expressing CD43 versus CD43-negative HeLa cells.
- Utilized antibody-blocking experiments to identify adhesion pathways involved.
- Assessed the impact of phorbol ester and neuraminidase treatments on cell adhesion.
Main Results:
- Significantly fewer T lymphocytes adhered to CD43-positive HeLa cells compared to CD43-negative cells.
- CD43-mediated inhibition of T-cell adhesion was linked to interference with LFA-1/ICAM-1 interactions.
- Neuraminidase treatment reduced the anti-adhesion effect of CD43, suggesting a role for its sialic acid residues.
Conclusions:
- CD43 expression on opposing cells can inhibit cell-cell adhesion.
- CD43 may regulate T-cell adhesion by modulating the LFA-1/ICAM-1 pathway, a key lymphocyte activation-induced adhesion mechanism.
Abstract:
CD43 is a cell-surface sialoglycoprotein of uncertain physiologic function expressed to various degrees by most leukocytes. We tested whether or not CD43 participates in intercellular adhesion by comparing the binding of human T lymphocytes to transfected HeLa cells stably expressing CD43 and sham-transfected HeLa cells (CD43-negative). Significantly fewer T lymphocytes adhered to the CD43-positive HeLa cells than to the CD43-negative HeLa cells. Diminished T-cell adherence to the CD43-positive HeLa cells was seen for all T lymphocytes tested, irrespective of their source or derivation. Antibody-blocking experiments revealed that CD43 interference with T-cell adhesion largely represented interference with T-cell leukocyte function-associated antigen 1 binding to HeLa cell intercellular adhesion molecule 1. The CD43 anti-adhesion effect was not overcome by treating cells with phorbol 12-myristate 13-acetate, a chemical that increases the binding avidity of leukocyte function-associated antigen 1 for intercellular adhesion molecule 1. However, neuraminidase treatment of the HeLa cell transfectants diminished the CD43 antiadhesion effect. These data indicate that CD43 expression by opposing cells can interfere with cell-cell adhesion. The data also suggest that CD43 might regulate T-cell adhesion by interfering with leukocyte function-associated 1 binding to intercellular adhesion molecule 1, a major activation-induced adhesion pathway among lymphocytes.