Related Experiment Videos
Inhibition of T cell activation by the extracellular matrix protein tenascin
T J Hemesath1, L S Marton, K Stefansson
1Committees on Immunology and Neurobiology, University of Chicago, IL 60637.
Abstract:
Tenascin (TN) is an extracellular matrix protein that is expressed widely in the fetus and sparingly in the adult, but reappears at high levels in certain areas of tissue insult such as tumor matrices and sites of wound healing. We show here that soluble TN inhibits proliferation of human T cells in response to alpha CD3 Ab co-immobilized with the extracellular matrix protein fibronectin (FN). TN also inhibits proliferation driven by alpha CD3/IL-2 or by phorbol ester/IL-2, and it prevents high level induction of IL-2R. The presence of TN in culture medium does not detectably alter the pattern of tyrosine phosphorylation resulting from T cell triggering with alpha CD3, but at later time points prevents the appearance of functional NF-AT1 transcription factor complexes in T cell nuclear extracts. These findings are consistent with the postulated role for TN as a natural antagonist to FN action, and suggest that T cell responses occurring at tissue sites in which TN is expressed could be influenced by its presence.
Insights
Tenascin (TN), an extracellular matrix protein, inhibits human T cell proliferation and IL-2 receptor induction. This suggests TN influences T cell responses at sites of tissue repair and in tumors.
Area of Science:
- Immunology
- Cell Biology
- Extracellular Matrix Biology
Background:
- Tenascin (TN) is an extracellular matrix protein found in fetal tissues, wound healing sites, and tumors.
- Its role in regulating immune cell function, particularly T cells, is not fully understood.
Purpose of the Study:
- To investigate the effect of Tenascin (TN) on human T cell proliferation and activation.
- To explore the molecular mechanisms underlying TN's influence on T cell responses.
Main Methods:
- Human T cells were cultured with soluble TN and stimulated using anti-CD3 antibody, IL-2, or phorbol ester.
- T cell proliferation, IL-2 receptor (IL-2R) induction, tyrosine phosphorylation, and NF-AT1 transcription factor complex formation were analyzed.
Main Results:
- Soluble TN significantly inhibited T cell proliferation induced by anti-CD3/fibronectin (FN), anti-CD3/IL-2, and phorbol ester/IL-2.
- TN prevented high-level induction of IL-2R and the appearance of functional NF-AT1 transcription factor complexes.
- TN did not alter early tyrosine phosphorylation patterns following T cell activation.
Conclusions:
- Tenascin (TN) acts as a natural antagonist to fibronectin (FN) in regulating T cell proliferation.
- TN can suppress T cell activation by inhibiting late-stage events like NF-AT1 complex formation.
- These findings suggest TN influences T cell-mediated immune responses at sites of tissue insult.