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RANTES-induced T cell activation correlates with CD3 expression

D J Dairaghi1, K S Soo, E R Oldham

  • 1Department of Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94306, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|April 29, 1998
PubMed
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The chemokine RANTES triggers a distinct two-phase calcium signal in T cells. High concentrations activate a tyrosine kinase pathway, mimicking T cell receptor stimulation and depending on T cell receptor presence.

Area of Science:

  • Immunology
  • Cell Signaling

Background:

  • Chemokines like RANTES are crucial for immune cell communication.
  • T cell activation involves complex signaling pathways, including G-protein and tyrosine kinase cascades.
  • RANTES exhibits unique signaling properties in T cells, distinct from other chemokines.

Purpose of the Study:

  • To investigate the unique biphasic signaling of RANTES in T cells.
  • To elucidate the role of T cell receptor (TCR) and CD3 expression in RANTES-mediated signaling.
  • To understand the mechanism behind RANTES' distinct T cell activation pathway.

Main Methods:

  • Utilized Jurkat T cell lines with varying CD3 expression levels.
  • Stimulated cells with RANTES and anti-CD3 monoclonal antibody (mAb).
  • Analyzed cytoplasmic Ca2+ signals and correlated responses with CD3 and TCR expression.

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Main Results:

  • Identified a RANTES-induced second phase of calcium signaling, dependent on tyrosine kinase activity and high RANTES concentrations (>100 nM).
  • Demonstrated that only CD3(high) Jurkat T cells responded to RANTES via this pathway.
  • Showed that RANTES-induced activation requires the T cell receptor (TCR), even with low-level RANTES-specific chemokine receptor expression.

Conclusions:

  • RANTES induces a unique biphasic calcium signal in T cells, with the second phase mimicking T cell receptor activation.
  • TCR signaling is essential for RANTES-mediated T cell activation, particularly in CD3(high) cells.
  • This TCR-dependent pathway contributes to RANTES' distinct signaling profile in T cells.