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Intercellular adhesion molecule-1/LFA-1 ligation favors human Th1 development
Hermelijn H Smits1, Esther C de Jong, Joost H N Schuitemaker
1Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, and Department of Molecular Cell Biology, Free University Medical Center, Amsterdam, The Netherlands.
Journal of Immunology (Baltimore, Md. : 1950)
|February 2, 2002
Summary
Ligation of LFA-1/ICAM-1 molecules on T cells drives Th1 polarization independently of IL-12. This mechanism, mediated by effector dendritic cells (DC1), involves extracellular signal-regulated kinase and may operate during viral infections.
Area of Science:
- Immunology
- Cellular Biology
- Molecular Biology
Background:
- T helper (Th) cell differentiation into Th1 or Th2 subtypes is primarily dictated by cytokines like IL-12 and IL-4.
- Cell surface molecule interactions between dendritic cells (DCs) and naive Th cells offer alternative pathways for Th cell polarization.
Purpose of the Study:
- To investigate the role of LFA-1/ICAM-1 ligation in human Th cell polarization.
- To explore an IL-12-independent mechanism of Th1 differentiation.
Main Methods:
- Stimulation of naive Th cells with immobilized Fc-ICAM-1 to trigger LFA-1.
- Co-culture of naive Th cells with effector DCs (DC1) generated by poly(I:C) maturation.
- Assessment of Th1/Th2 polarization markers (T-bet, GATA-3) and cytokine levels.
- Inhibition of extracellular signal-regulated kinase (ERK) phosphorylation.
Main Results:
- LFA-1/ICAM-1 ligation on Th cells induced Th1 polarization, decreasing GATA-3 and increasing T-bet expression, particularly under low cytokine conditions.
- Poly(I:C)-matured DCs (DC1), expressing high ICAM-1 and low IL-12p70, exhibited Th1-driving capacity.
- Blocking ICAM-1/LFA-1 interaction reduced the Th1-driving capacity of DC1.
- ERK phosphorylation inhibition blocked LFA-1-mediated Th1 differentiation.
Conclusions:
- A novel IL-12-independent mechanism for Th1 polarization exists, mediated by LFA-1/ICAM-1 ligation and ERK signaling.
- Effector DCs (DC1) can drive Th1 polarization through this pathway, potentially relevant during viral infections.