Skip to main content
Top
Published in: BMC Immunology 1/2015

Open Access 01-12-2015 | Research article

Morphological change of CD4+ T cell during contact with DC modulates T-cell activation by accumulation of F-actin in the immunology synapse

Authors: Wei Lin, Yuanzhen Suo, Yuting Deng, Zhichao Fan, Yijie Zheng, Xunbin Wei, Yiwei Chu

Published in: BMC Immunology | Issue 1/2015

Login to get access

Abstract

Background

The changes in T-cell morphology during immunological synapse (IS) formation are essential for T-cell activation. Previous researches have shown that T cell changed from spherical to elongated and/or flattened during in contact with B cell. As most powerful antigen presenting cell, dendritic cell (DC) has a strong ability to activate T cells. However, the morphological change of T cell which contacts DC and the relationship between morphological change and T-cell activation are not very clear. Thus, we studied the morphological change of CD4+ T cell during contact with DC.

Results

Using live-cell imaging, we discovered diversity in the T-cell morphological changes during contact with DCs. The elongation-flattening of CD4+ T cells correlated with a low-level Ca2+ response and a loss of T-cell receptor (TCR) signalling molecules in the IS, including zeta-chain associated protein kinase 70 (ZAP-70), phospholipase C-γ (PLC-γ) and protein kinase C-θ (PKC-θ), whereas rounding-flattening correlated with sufficient CD4+ T-cell activation. Different morphological changes were correlated with the different amount of accumulated filamentous actin (F-actin) in the IS. Disruption of F-actin by cytochalasin D impaired the morphological change and the localisation of calcium microdomains in the IS and decreased the calcium response in CD4+ T cells.

Conclusion

Our study discovered the diversity in morphological change of T cells during contacted with DCs. During this process, the different morphological changes of T cells modulate T-cell activation by the different amount of F-actin accumulation in the IS, which controls the distribution of calcium microdomains to affect T-cell activation.
Appendix
Available only for authorised users
Literature
1.
go back to reference Grakoui A, Bromley SK, Sumen C, Davis MM, Shaw AS, Allen PM, et al. The immunological synapse: a molecular machine controlling T cell activation. Science. 1999;285:221–7.CrossRefPubMed Grakoui A, Bromley SK, Sumen C, Davis MM, Shaw AS, Allen PM, et al. The immunological synapse: a molecular machine controlling T cell activation. Science. 1999;285:221–7.CrossRefPubMed
2.
go back to reference Xu H, Li X, Liu D, Li J, Zhang X, Chen X, et al. Follicular T-helper cell recruitment governed by bystander B cells and ICOS-driven motility. Nature. 2013;496:523–7.CrossRefPubMed Xu H, Li X, Liu D, Li J, Zhang X, Chen X, et al. Follicular T-helper cell recruitment governed by bystander B cells and ICOS-driven motility. Nature. 2013;496:523–7.CrossRefPubMed
3.
go back to reference Lafouresse F, Cotta-de-Almeida V, Malet-Engra G, Galy A, Valitutti S, Dupre L. Wiskott-Aldrich syndrome protein controls antigen-presenting cell-driven CD4+ T-cell motility by regulating adhesion to intercellular adhesion molecule-1. Immunology. 2012;137:183–96.PubMedCentralCrossRefPubMed Lafouresse F, Cotta-de-Almeida V, Malet-Engra G, Galy A, Valitutti S, Dupre L. Wiskott-Aldrich syndrome protein controls antigen-presenting cell-driven CD4+ T-cell motility by regulating adhesion to intercellular adhesion molecule-1. Immunology. 2012;137:183–96.PubMedCentralCrossRefPubMed
4.
go back to reference Depoil D, Zaru R, Guiraud M, Chauveau A, Harriague J, Bismuth G, et al. Immunological synapses are versatile structures enabling selective T cell polarization. Immunity. 2005;22:185–94.CrossRefPubMed Depoil D, Zaru R, Guiraud M, Chauveau A, Harriague J, Bismuth G, et al. Immunological synapses are versatile structures enabling selective T cell polarization. Immunity. 2005;22:185–94.CrossRefPubMed
5.
go back to reference Wulfing C, Davis MM. A receptor/cytoskeletal movement triggered by costimulation during T cell activation. Science. 1998;282:2266–9.CrossRefPubMed Wulfing C, Davis MM. A receptor/cytoskeletal movement triggered by costimulation during T cell activation. Science. 1998;282:2266–9.CrossRefPubMed
6.
go back to reference Joseph N, Reicher B, Barda-Saad M. The calcium feedback loop and T cell activation: How cytoskeleton networks control intracellular calcium flux. Biochim Biophys Acta. 2013;1838:557–68.CrossRefPubMed Joseph N, Reicher B, Barda-Saad M. The calcium feedback loop and T cell activation: How cytoskeleton networks control intracellular calcium flux. Biochim Biophys Acta. 2013;1838:557–68.CrossRefPubMed
7.
go back to reference Wei X, Tromberg BJ, Cahalan MD. Mapping the sensitivity of T cells with an optical trap: polarity and minimal number of receptors for Ca(2+) signaling. Proc Natl Acad Sci U S A. 1999;96:8471–6.PubMedCentralCrossRefPubMed Wei X, Tromberg BJ, Cahalan MD. Mapping the sensitivity of T cells with an optical trap: polarity and minimal number of receptors for Ca(2+) signaling. Proc Natl Acad Sci U S A. 1999;96:8471–6.PubMedCentralCrossRefPubMed
8.
go back to reference Delon J, Bercovici N, Liblau R, Trautmann A. Imaging antigen recognition by naive CD4+ T cells: compulsory cytoskeletal alterations for the triggering of an intracellular calcium response. Eur J Immunol. 1998;28:716–29.CrossRefPubMed Delon J, Bercovici N, Liblau R, Trautmann A. Imaging antigen recognition by naive CD4+ T cells: compulsory cytoskeletal alterations for the triggering of an intracellular calcium response. Eur J Immunol. 1998;28:716–29.CrossRefPubMed
9.
go back to reference Faure S, Salazar-Fontana LI, Semichon M, Tybulewicz VL, Bismuth G, Trautmann A, et al. ERM proteins regulate cytoskeleton relaxation promoting T cell-APC conjugation. Nat Immunol. 2004;5:272–9.CrossRefPubMed Faure S, Salazar-Fontana LI, Semichon M, Tybulewicz VL, Bismuth G, Trautmann A, et al. ERM proteins regulate cytoskeleton relaxation promoting T cell-APC conjugation. Nat Immunol. 2004;5:272–9.CrossRefPubMed
10.
go back to reference Donnadieu E, Bismuth G, Trautmann A. Antigen recognition by helper T cells elicits a sequence of distinct changes of their shape and intracellular calcium. Curr Biol. 1994;4:584–95.CrossRefPubMed Donnadieu E, Bismuth G, Trautmann A. Antigen recognition by helper T cells elicits a sequence of distinct changes of their shape and intracellular calcium. Curr Biol. 1994;4:584–95.CrossRefPubMed
11.
go back to reference Negulescu PA, Krasieva TB, Khan A, Kerschbaum HH, Cahalan MD. Polarity of T cell shape, motility, and sensitivity to antigen. Immunity. 1996;4:421–30.CrossRefPubMed Negulescu PA, Krasieva TB, Khan A, Kerschbaum HH, Cahalan MD. Polarity of T cell shape, motility, and sensitivity to antigen. Immunity. 1996;4:421–30.CrossRefPubMed
12.
go back to reference Brossard C, Feuillet V, Schmitt A, Randriamampita C, Romao M, Raposo G, et al. Multifocal structure of the T cell - dendritic cell synapse. Eur J Immunol. 2005;35:1741–53.CrossRefPubMed Brossard C, Feuillet V, Schmitt A, Randriamampita C, Romao M, Raposo G, et al. Multifocal structure of the T cell - dendritic cell synapse. Eur J Immunol. 2005;35:1741–53.CrossRefPubMed
13.
go back to reference Lin W, Fan Z, Suo Y, Deng Y, Zhang M, Wang J, et al. The bullseye synapse formed between CD4+ T-cell and staphylococcal enterotoxin B-pulsed dendritic cell is a suppressive synapse in T-cell response. Immunol Cell Biol. 2015;93:99–110.CrossRefPubMed Lin W, Fan Z, Suo Y, Deng Y, Zhang M, Wang J, et al. The bullseye synapse formed between CD4+ T-cell and staphylococcal enterotoxin B-pulsed dendritic cell is a suppressive synapse in T-cell response. Immunol Cell Biol. 2015;93:99–110.CrossRefPubMed
15.
go back to reference Gorman JA, Babich A, Dick CJ, Schoon RA, Koenig A, Gomez TS, et al. The cytoskeletal adaptor protein IQGAP1 regulates TCR-mediated signaling and filamentous actin dynamics. J Immunol. 2012;188:6135–44.PubMedCentralCrossRefPubMed Gorman JA, Babich A, Dick CJ, Schoon RA, Koenig A, Gomez TS, et al. The cytoskeletal adaptor protein IQGAP1 regulates TCR-mediated signaling and filamentous actin dynamics. J Immunol. 2012;188:6135–44.PubMedCentralCrossRefPubMed
16.
go back to reference Yokosuka T, Sakata-Sogawa K, Kobayashi W, Hiroshima M, Hashimoto-Tane A, Tokunaga M, et al. Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76. Nat Immunol. 2005;6:1253–62.CrossRefPubMed Yokosuka T, Sakata-Sogawa K, Kobayashi W, Hiroshima M, Hashimoto-Tane A, Tokunaga M, et al. Newly generated T cell receptor microclusters initiate and sustain T cell activation by recruitment of Zap70 and SLP-76. Nat Immunol. 2005;6:1253–62.CrossRefPubMed
17.
18.
19.
go back to reference Quintana A, Pasche M, Junker C, Al-Ansary D, Rieger H, Kummerow C, et al. Calcium microdomains at the immunological synapse: how ORAI channels, mitochondria and calcium pumps generate local calcium signals for efficient T-cell activation. Embo J. 2011;30:3895–912.PubMedCentralCrossRefPubMed Quintana A, Pasche M, Junker C, Al-Ansary D, Rieger H, Kummerow C, et al. Calcium microdomains at the immunological synapse: how ORAI channels, mitochondria and calcium pumps generate local calcium signals for efficient T-cell activation. Embo J. 2011;30:3895–912.PubMedCentralCrossRefPubMed
20.
go back to reference Quintana A, Hoth M. Mitochondrial dynamics and their impact on T cell function. Cell Calcium. 2012;52:57–63.CrossRefPubMed Quintana A, Hoth M. Mitochondrial dynamics and their impact on T cell function. Cell Calcium. 2012;52:57–63.CrossRefPubMed
21.
go back to reference Qu B, Al-Ansary D, Kummerow C, Hoth M, Schwarz EC. ORAI-mediated calcium influx in T cell proliferation, apoptosis and tolerance. Cell Calcium. 2011;50:261–9.CrossRefPubMed Qu B, Al-Ansary D, Kummerow C, Hoth M, Schwarz EC. ORAI-mediated calcium influx in T cell proliferation, apoptosis and tolerance. Cell Calcium. 2011;50:261–9.CrossRefPubMed
22.
go back to reference Tseng SY, Waite JC, Liu M, Vardhana S, Dustin ML. T cell-dendritic cell immunological synapses contain TCR-dependent CD28-CD80 clusters that recruit protein kinase C theta. J Immunol. 2008;181:4852–63.PubMedCentralCrossRefPubMed Tseng SY, Waite JC, Liu M, Vardhana S, Dustin ML. T cell-dendritic cell immunological synapses contain TCR-dependent CD28-CD80 clusters that recruit protein kinase C theta. J Immunol. 2008;181:4852–63.PubMedCentralCrossRefPubMed
23.
go back to reference Shen Z, Reznikoff G, Dranoff G, Rock KL. Cloned dendritic cells can present exogenous antigens on both MHC class I and class II molecules. J Immunol. 1997;158:2723–30.PubMed Shen Z, Reznikoff G, Dranoff G, Rock KL. Cloned dendritic cells can present exogenous antigens on both MHC class I and class II molecules. J Immunol. 1997;158:2723–30.PubMed
24.
go back to reference Quintana A, Schwindling C, Wenning AS, Becherer U, Rettig J, Schwarz EC, et al. T cell activation requires mitochondrial translocation to the immunological synapse. Proc Natl Acad Sci U S A. 2007;104:14418–23.PubMedCentralCrossRefPubMed Quintana A, Schwindling C, Wenning AS, Becherer U, Rettig J, Schwarz EC, et al. T cell activation requires mitochondrial translocation to the immunological synapse. Proc Natl Acad Sci U S A. 2007;104:14418–23.PubMedCentralCrossRefPubMed
25.
go back to reference Takahashi A, Camacho P, Lechleiter JD, Herman B. Measurement of intracellular calcium. Physiol Rev. 1999;79:1089–125.PubMed Takahashi A, Camacho P, Lechleiter JD, Herman B. Measurement of intracellular calcium. Physiol Rev. 1999;79:1089–125.PubMed
26.
go back to reference Thiel M, Wolfs MJ, Bauer S, Wenning AS, Burckhart T, Schwarz EC, et al. Efficiency of T-cell costimulation by CD80 and CD86 cross-linking correlates with calcium entry. Immunology. 2010;129:28–40.PubMedCentralCrossRefPubMed Thiel M, Wolfs MJ, Bauer S, Wenning AS, Burckhart T, Schwarz EC, et al. Efficiency of T-cell costimulation by CD80 and CD86 cross-linking correlates with calcium entry. Immunology. 2010;129:28–40.PubMedCentralCrossRefPubMed
27.
go back to reference Quintana A, Kummerow C, Junker C, Becherer U, Hoth M. Morphological changes of T cells following formation of the immunological synapse modulate intracellular calcium signals. Cell Calcium. 2009;45:109–22.CrossRefPubMed Quintana A, Kummerow C, Junker C, Becherer U, Hoth M. Morphological changes of T cells following formation of the immunological synapse modulate intracellular calcium signals. Cell Calcium. 2009;45:109–22.CrossRefPubMed
28.
go back to reference Thastrup O, Cullen PJ, Drobak BK, Hanley MR, Dawson AP. Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2(+)-ATPase. Proc Natl Acad Sci U S A. 1990;87:2466–70.PubMedCentralCrossRefPubMed Thastrup O, Cullen PJ, Drobak BK, Hanley MR, Dawson AP. Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2(+)-ATPase. Proc Natl Acad Sci U S A. 1990;87:2466–70.PubMedCentralCrossRefPubMed
29.
go back to reference Bautista DM, Hoth M, Lewis RS. Enhancement of calcium signalling dynamics and stability by delayed modulation of the plasma-membrane calcium-ATPase in human T cells. J Physiol. 2002;541:877–94.PubMedCentralCrossRefPubMed Bautista DM, Hoth M, Lewis RS. Enhancement of calcium signalling dynamics and stability by delayed modulation of the plasma-membrane calcium-ATPase in human T cells. J Physiol. 2002;541:877–94.PubMedCentralCrossRefPubMed
30.
go back to reference Monks CR, Freiberg BA, Kupfer H, Sciaky N, Kupfer A. Three-dimensional segregation of supramolecular activation clusters in T cells. Nature. 1998;395:82–6.CrossRefPubMed Monks CR, Freiberg BA, Kupfer H, Sciaky N, Kupfer A. Three-dimensional segregation of supramolecular activation clusters in T cells. Nature. 1998;395:82–6.CrossRefPubMed
31.
go back to reference Bubeck Wardenburg J, Pappu R, Bu JY, Mayer B, Chernoff J, Straus D, et al. Regulation of PAK activation and the T cell cytoskeleton by the linker protein SLP-76. Immunity. 1998;9:607–16.CrossRefPubMed Bubeck Wardenburg J, Pappu R, Bu JY, Mayer B, Chernoff J, Straus D, et al. Regulation of PAK activation and the T cell cytoskeleton by the linker protein SLP-76. Immunity. 1998;9:607–16.CrossRefPubMed
32.
go back to reference Villalba M, Coudronniere N, Deckert M, Teixeiro E, Mas P, Altman A. A novel functional interaction between Vav and PKCtheta is required for TCR-induced T cell activation. Immunity. 2000;12:151–60.CrossRefPubMed Villalba M, Coudronniere N, Deckert M, Teixeiro E, Mas P, Altman A. A novel functional interaction between Vav and PKCtheta is required for TCR-induced T cell activation. Immunity. 2000;12:151–60.CrossRefPubMed
33.
go back to reference Babich A, Li S, O’Connor RS, Milone MC, Freedman BD, Burkhardt JK. F-actin polymerization and retrograde flow drive sustained PLCgamma1 signaling during T cell activation. J Cell Biol. 2012;197:775–87.PubMedCentralCrossRefPubMed Babich A, Li S, O’Connor RS, Milone MC, Freedman BD, Burkhardt JK. F-actin polymerization and retrograde flow drive sustained PLCgamma1 signaling during T cell activation. J Cell Biol. 2012;197:775–87.PubMedCentralCrossRefPubMed
34.
go back to reference Nolz JC, Gomez TS, Zhu P, Li S, Medeiros RB, Shimizu Y, et al. The WAVE2 complex regulates actin cytoskeletal reorganization and CRAC-mediated calcium entry during T cell activation. Curr Biol. 2006;16:24–34.PubMedCentralCrossRefPubMed Nolz JC, Gomez TS, Zhu P, Li S, Medeiros RB, Shimizu Y, et al. The WAVE2 complex regulates actin cytoskeletal reorganization and CRAC-mediated calcium entry during T cell activation. Curr Biol. 2006;16:24–34.PubMedCentralCrossRefPubMed
35.
go back to reference Quintana A, Schwarz EC, Schwindling C, Lipp P, Kaestner L, Hoth M. Sustained activity of calcium release-activated calcium channels requires translocation of mitochondria to the plasma membrane. J Biol Chem. 2006;281:40302–9.CrossRefPubMed Quintana A, Schwarz EC, Schwindling C, Lipp P, Kaestner L, Hoth M. Sustained activity of calcium release-activated calcium channels requires translocation of mitochondria to the plasma membrane. J Biol Chem. 2006;281:40302–9.CrossRefPubMed
36.
go back to reference Lioudyno MI, Kozak JA, Penna A, Safrina O, Zhang SL, Sen D, et al. Orai1 and STIM1 move to the immunological synapse and are up-regulated during T cell activation. Proc Natl Acad Sci U S A. 2008;105:2011–6.PubMedCentralCrossRefPubMed Lioudyno MI, Kozak JA, Penna A, Safrina O, Zhang SL, Sen D, et al. Orai1 and STIM1 move to the immunological synapse and are up-regulated during T cell activation. Proc Natl Acad Sci U S A. 2008;105:2011–6.PubMedCentralCrossRefPubMed
37.
go back to reference Babich A, Burkhardt JK. Coordinate control of cytoskeletal remodeling and calcium mobilization during T-cell activation. Immunol Rev. 2013;256:80–94.CrossRefPubMed Babich A, Burkhardt JK. Coordinate control of cytoskeletal remodeling and calcium mobilization during T-cell activation. Immunol Rev. 2013;256:80–94.CrossRefPubMed
38.
go back to reference Kummerow C, Junker C, Kruse K, Rieger H, Quintana A, Hoth M. The immunological synapse controls local and global calcium signals in T lymphocytes. Immunol Rev. 2009;231:132–47.CrossRefPubMed Kummerow C, Junker C, Kruse K, Rieger H, Quintana A, Hoth M. The immunological synapse controls local and global calcium signals in T lymphocytes. Immunol Rev. 2009;231:132–47.CrossRefPubMed
39.
go back to reference Schell MJ, Irvine RF. Calcium-triggered exit of F-actin and IP(3) 3-kinase A from dendritic spines is rapid and reversible. Eur J Neurosci. 2006;24:2491–503.CrossRefPubMed Schell MJ, Irvine RF. Calcium-triggered exit of F-actin and IP(3) 3-kinase A from dendritic spines is rapid and reversible. Eur J Neurosci. 2006;24:2491–503.CrossRefPubMed
40.
go back to reference Wei B, da Rocha Dias S, Wang H, Rudd CE. CTL-associated antigen-4 ligation induces rapid T cell polarization that depends on phosphatidylinositol 3-kinase, Vav-1, Cdc42, and myosin light chain kinase. J Immunol. 2007;179:400–8.CrossRefPubMed Wei B, da Rocha Dias S, Wang H, Rudd CE. CTL-associated antigen-4 ligation induces rapid T cell polarization that depends on phosphatidylinositol 3-kinase, Vav-1, Cdc42, and myosin light chain kinase. J Immunol. 2007;179:400–8.CrossRefPubMed
41.
go back to reference Wong NK, Lai JC, Maeshima N, Johnson P. CD44-mediated elongated T cell spreading requires Pyk2 activation by Src family kinases, extracellular calcium, phospholipase C and phosphatidylinositol-3 kinase. Cell Signal. 2011;23:812–9.CrossRefPubMed Wong NK, Lai JC, Maeshima N, Johnson P. CD44-mediated elongated T cell spreading requires Pyk2 activation by Src family kinases, extracellular calcium, phospholipase C and phosphatidylinositol-3 kinase. Cell Signal. 2011;23:812–9.CrossRefPubMed
42.
go back to reference Lek HS, Morrison VL, Conneely M, Campbell PA, McGloin D, Kliche S, et al. The spontaneously adhesive leukocyte function-associated antigen-1 (LFA-1) integrin in effector T cells mediates rapid actin- and calmodulin-dependent adhesion strengthening to ligand under shear flow. J Biol Chem. 2013;288:14698–708.PubMedCentralCrossRefPubMed Lek HS, Morrison VL, Conneely M, Campbell PA, McGloin D, Kliche S, et al. The spontaneously adhesive leukocyte function-associated antigen-1 (LFA-1) integrin in effector T cells mediates rapid actin- and calmodulin-dependent adhesion strengthening to ligand under shear flow. J Biol Chem. 2013;288:14698–708.PubMedCentralCrossRefPubMed
43.
go back to reference Porter JC, Bracke M, Smith A, Davies D, Hogg N. Signaling through integrin LFA-1 leads to filamentous actin polymerization and remodeling, resulting in enhanced T cell adhesion. J Immunol. 2002;168:6330–5.CrossRefPubMed Porter JC, Bracke M, Smith A, Davies D, Hogg N. Signaling through integrin LFA-1 leads to filamentous actin polymerization and remodeling, resulting in enhanced T cell adhesion. J Immunol. 2002;168:6330–5.CrossRefPubMed
Metadata
Title
Morphological change of CD4+ T cell during contact with DC modulates T-cell activation by accumulation of F-actin in the immunology synapse
Authors
Wei Lin
Yuanzhen Suo
Yuting Deng
Zhichao Fan
Yijie Zheng
Xunbin Wei
Yiwei Chu
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2015
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/s12865-015-0108-x

Other articles of this Issue 1/2015

BMC Immunology 1/2015 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.