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Evidence for a novel function of the CD40 ligand as a signalling molecule in T-lymphocytes
B Brenner1, U Koppenhoefer, H Grassmé
1Department of Physiology, University of Tübingen, Germany.
Insights
The CD40 ligand (gp39/CD40L) activates T-lymphocytes by stimulating Jun-N-terminal kinase (JNK) and p38 kinases. This pathway involves p56(lck) and Rac1, crucial for T-cell activation.
Area of Science:
- Immunology
- Cell Signaling
Background:
- CD40 receptor-ligand interaction is vital for B-lymphocyte activation.
- The role of gp39/CD40L in T-lymphocyte activation requires further elucidation.
Purpose of the Study:
- To investigate the function of gp39/CD40L as a stimulatory molecule for T-lymphocytes.
- To identify the signaling pathways involved in gp39/CD40L-mediated T-lymphocyte activation.
Main Methods:
- T-lymphocyte activation assays using gp39/CD40L.
- Western blotting to detect kinase activation (JNK, p38-K, p56(lck)).
- Rac1 activity assays and inhibition studies.
- Analysis of protein tyrosine phosphorylation.
Main Results:
- gp39/CD40L robustly activates T-lymphocytes, inducing JNK and p38-K activation.
- Rac1 activation correlates with JNK/p38-K stimulation; Rac1 inhibition blocks this activation.
- CD40 ligand stimulation leads to protein tyrosine phosphorylation and p56(lck) activation.
- Inhibition of src-like kinases impairs Rac1 and JNK/p38-K activation.
Conclusions:
- gp39/CD40L acts as a potent stimulatory molecule for T-lymphocytes.
- A signaling cascade involving p56(lck) and Rac1 mediates gp39/CD40L-induced JNK/p38-K activation in T-cells.
Abstract:
The interaction of the CD40 receptor with its ligand has been shown to be crucial for the activation of B-lymphocytes. Here, we provide evidence that the pg39 molecule/CD40 ligand (gp39/CD40L) also functions as a stimulatory molecule for T-lymphocytes. Activation of T-lymphocytes via gp39/CD40L induced a strong activation of Jun-N-terminal kinase (JNK) and p38-K. Activation of these kinases correlates with a stimulation of Rac1 and inhibition of Rac1 prevents gp39/CD40L triggered JNK/p38-K activation. Further, cellular stimulation via the CD40 ligand results in tyrosine phosphorylation of cellular proteins and the activation of p56(lck). Inhibition of src-like kinases inhibits Rac1 as well as JNK/p38-K stimulation suggesting a signalling cascade from the gp39/CD40L via p56(lck) and Rac1 to JNK/p38-K.