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NFAT即活化T细胞核因子，当Th1细胞受到tcr活化刺激时，依次引起膜微区改变、钙离子信号转导、NFAT活化。程度明显高于Th2。
Membrane expression and distribution of gangliosides, cholesterol and the TCR/CD3 complex in polariz ...
Figure 3. Membrane expression and distribution of gangliosides, cholesterol and the TCR/CD3 complex in polarized Th cells. Confocal microscopic images show the colocalization of TCR/CD3 (green) and GM1 gangliosides (red) in quiescent and activated Th0 (A, B), Th1 (C, D) or Th2 (E, F) cells. G: Pearson’s coefficients quantifying colocalization levels in quiescent and activated cells (significance (*): P 0.05). H: Concentration dependence of choleratoxin-B binding to Th0 (triangle), Th1 (square) and Th2 (circle) cells. Data are displayed as mean SD from four independent measurements. I: Membrane cholesterol levels of Th hybridomas, detected with anti-cholesterol mAb (AC8), are shown as relative mean fluorescence intensity (RMF) SD from three independent measurements.
Membrane microdomain organization, calcium signal, and NFAT activation as an important axis in polarized Th cell function.AuthorsIzsepi E, Himer L, Szilagyi O, Hajdu P, Panyi G, Laszlo G, Matko J.
JournalCytometry A. 2012 Nov 26. doi: 10.1002/cyto.a.22234. [Epub ahead of print] AffiliationDepartment of Immunology, Eötvös Lorand University, Budapest, Hungary.
AbstractT 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 Ca(2+) -response in Th1 cells compared to Th2 ones correlates well with a shorter nuclear residence time of the Ca(2+) -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 Ca(2+) -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-Ca(2+) -signaling-NFAT activation axis is an important determinant of polarized Th cell effector function and fate. © 2012 International Society for Advancement of Cytometry. Copyright © 2012 International Society for Advancement of Cytometry.
PMID 23184643 [PubMed - as supplied by publisher]
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发表于 2012-12-3 22:27:31
发表于 2012-12-13 09:59:29
