Membrane microdomain organization, calcium signal, and NFAT activation as an important axis in polarized Th cell function

Emese Izsepi, Leonora Himer, Orsolya Szilagyi, Peter Hajdu, G. Panyi, Gloria Laszlo, J. Matkó

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

T helper lymphocytes become polarized upon antigen and cytokine stimuli received after their maturation in the thymus. Since the balance of Th1 and Th2 responses is critical in healthy and pathological immune responses, understanding the molecular base of T cell polarization still remained an important question. Using our Th0/Th1/Th2 hybridoma model system, we performed a comparative study on polarized Th1 and Th2 cells in terms of their membrane raft expression/composition, their TCR mediated activation signaling, and sensitivity to activation-induced cell death (AICD) using flow and image cytometric methods. We show here that the TCR stimulation induced more intense and sustained Ca2+-response in Th1 cells compared to Th2 ones correlates well with a shorter nuclear residence time of the Ca2+-dependent NFAT transcription factor in Th2 cells. In addition, NFAT translocation directly depended on lipid raft integrity/membrane cholesterol level. Expression pattern of raftophilic accessory proteins (CD4, CD59, and CD48) and lipids (GM1, cholesterol) were also different in the Th1 and Th2 hybridomas, similarly to differentiated spleen Th cells. The activation-induced, remarkably clustered and polarized membrane distribution of TCR/CD3 complex in Th1, but not in Th2 cells, together with an increased raft localization of Kv1.3 ion channels regulating the Ca2+-response, are consistent with the above properties of NFAT. Finally, the polarized Th cells, especially Th1, were more sensitive to AICD than their unpolarized Th0 precursor. These results suggest that the membrane microdomain organization-Ca2+-signaling-NFAT activation axis is an important determinant of polarized Th cell effector function and fate.

Original languageEnglish
Pages (from-to)185-196
Number of pages12
JournalCytometry Part A
Volume83 A
Issue number2
DOIs
Publication statusPublished - Feb 2013

Fingerprint

Membrane Microdomains
Th2 Cells
Th1 Cells
Hybridomas
Calcium
Membranes
Cell Death
T-Cell Antigen Receptor-CD3 Complex
Cholesterol
Th1-Th2 Balance
Lipids
Helper-Inducer T-Lymphocytes
Ion Channels
Thymus Gland
Transcription Factors
Spleen
Cytokines
T-Lymphocytes
Antigens
Proteins

Keywords

  • Cell death sensitivity
  • Cytokine profiles
  • Differential Ca-signals
  • Ion channels
  • Lipid rafts
  • NFAT
  • T cell polarization
  • Th1 cells
  • Th2 cells

ASJC Scopus subject areas

  • Cell Biology
  • Histology
  • Pathology and Forensic Medicine

Cite this

Membrane microdomain organization, calcium signal, and NFAT activation as an important axis in polarized Th cell function. / Izsepi, Emese; Himer, Leonora; Szilagyi, Orsolya; Hajdu, Peter; Panyi, G.; Laszlo, Gloria; Matkó, J.

In: Cytometry Part A, Vol. 83 A, No. 2, 02.2013, p. 185-196.

Research output: Contribution to journalArticle

Izsepi, Emese ; Himer, Leonora ; Szilagyi, Orsolya ; Hajdu, Peter ; Panyi, G. ; Laszlo, Gloria ; Matkó, J. / Membrane microdomain organization, calcium signal, and NFAT activation as an important axis in polarized Th cell function. In: Cytometry Part A. 2013 ; Vol. 83 A, No. 2. pp. 185-196.
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