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Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes
Published on: June 13, 2014
Functional analysis of intercellular adhesion molecule-1-expressing human thyroid cells
A P Weetman1, M Freeman, L K Borysiewicz
1Department of Medicine, University of Cambridge Clinical School, Addenbrooke's Hospital, Cambridge, GB.
Insights
Thyroid cells express intercellular adhesion molecule-1 (ICAM-1), enhancing immune cell recognition and cytotoxicity. This ICAM-1 role may contribute to the development and progression of autoimmune thyroiditis.
Area of Science:
- Immunology
- Endocrinology
- Cell Biology
Background:
- Intercellular adhesion molecule-1 (ICAM-1) is implicated in immune cell interactions.
- The specific role of ICAM-1 in thyroid cells during autoimmune processes requires further elucidation.
Purpose of the Study:
- To investigate the expression and function of ICAM-1 in thyroid cells.
- To determine the impact of ICAM-1 on immune cell clustering and cytotoxicity against thyroid cells.
Main Methods:
- In vitro assays including cell clustering and cytotoxicity measurements.
- Stimulation of thyroid cells with cytokines (e.g., interferon-gamma) and lymphocytes.
- Flow cytometry to assess lymphocyte-thyroid cell cluster formation.
- Use of monoclonal antibodies against ICAM-1 to block its function.
Main Results:
- Thyroid cell ICAM-1 expression increased upon cytokine stimulation within 24 hours, unaffected by methimazole.
- Anti-ICAM-1 antibody reduced lymphocyte-thyroid cell cluster formation by approximately one-third.
- Phytohemagglutinin-stimulated lymphocyte cytotoxicity against thyroid cells decreased by 23%-28% in the presence of anti-ICAM-1 antibody.
- Thyroid cells demonstrated rhinovirus infection, confirming functional ICAM-1 ligand presence.
Conclusions:
- Thyroid cell ICAM-1 expression can enhance immune cell recognition and contribute to cytotoxicity.
- These ICAM-1 functions may play a significant role in the initiation or perpetuation of autoimmune thyroiditis.
Abstract:
We have tested the potential role of thyroid cell intercellular adhesion molecule-1 (ICAM-1) expression by in vitro assays of cell clustering and cytotoxicity. Increased ICAM-1 appeared within 24 h of thyroid cell stimulation with cytokines and was not inhibited by the antithyroid drug methimazole. Autologous and allogeneic lymphocyte-thyroid cell cluster formation, assessed by flow cytometry, was reduced by about one-third in the presence of a monoclonal antibody against ICAM-1, regardless of whether thyroid cells were expressing basal levels of ICAM-1 or had been stimulated with interferon-gamma. The cytotoxicity produced by interleukin 2-stimulated allogeneic lymphocytes was not consistently inhibited by anti-ICAM-1 antibody, but phytohemagglutinin-stimulated lymphocytes showed a reduction of 23%-28% in cytotoxicity against untreated or interferon-gamma stimulated thyroid cells when the anti-ICAM-1 monoclonal antibody was present. Finally, thyroid cells could be infected by rhinovirus, confirming the presence of fully functional ligand. These results show that ICAM-1 expression by thyroid cells may enhance immune cell recognition and play some role in cytotoxicity, features which could be important in the initiation or perpetuation of autoimmune thyroiditis.
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