Acta Physiologica Hungarica
Volume/Issue:
Volume 102: Issue 2
Altered mitochondrial response to activation of T-cells in neonate
Authors:
G Mészáros

Search for other papers by G Mészáros in
Current site
Google Scholar
PubMed Close
,
Cs Orbán MTA-SE, Pediatrics and Nephrology Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary

Search for other papers by Cs Orbán in
Current site
Google Scholar
PubMed Close
,
A Kaposi MTA-SE, Pediatrics and Nephrology Research Group, Hungarian Academy of Sciences, Semmelweis University, Budapest, Hungary

Search for other papers by A Kaposi in
Current site
Google Scholar
PubMed Close
,
G Toldi

Search for other papers by G Toldi in
Current site
Google Scholar
PubMed Close
,
B Gyarmati Department of Obstetrics and Gynaecology, Uzsoki Street Hospital, Budapest, Hungary

Search for other papers by B Gyarmati in
Current site
Google Scholar
PubMed Close
,
T Tulassay

Search for other papers by T Tulassay in
Current site
Google Scholar
PubMed Close
, and
Prof. Barna Vásárhelyi

Search for other papers by Prof. Barna Vásárhelyi in
Current site
Google Scholar
PubMed Close
Pages:
216–227
Online Publication Date:
Jun 2015
Publication Date:
01 Jun 2015
Article Category:
Research Article
DOI:
https://doi.org/10.1556/036.102.2015.2.12
Keywords:
calcium; flow cytometry; mitochondrial membrane potential; neonate; superoxide; T-cell
Restricted access

Mitochondrial functions have a major impact on T-cell functionality. In this study we characterized whether mitochondrial function in the neonatal T-cells differs from that in the adult T-cells during short T-cell activation. Methods: We used fow cytometry methods to test mitochondrial mass and to monitor mitochondrial Ca2+ levels, mitochondrial potential and superoxide generation in parallel with cytoplasmic Ca2+ levels during phythohaemagglutinine-induced activation of CD4+ and CD8+ T-cells of 12 term neonates and 11 healthy adults. Results: Baseline mitochondrial mass of CD4+ and CD8+ cells was lower in the neonate than in the adult. In comparison with the adult, neonatal resting CD4+ T-cells had lower cytoplasmic Ca2+ levels and this was associated with normal activation induced Ca2+-response. During short-term activation cytoplasmic Ca2+-response was lower in neonatal than in adult CD8+ T-cells. Mitochondrial Ca2+ uptake was increased in CD4+ neonatal T cells while it decreased in CD8+ T-cells. Mitochondrial depolarization was increased in CD4+ and decreased in CD8+ neonatal T-cells compared to adults. Superoxide generation was higher and equal in neonatal CD4+ and CD8+ cells, respectively, compared to the adult ones. Conclusion: Our data suggest that neonatal T-cells exhibit marked differences in mitochondrial function and superoxide generation compared to adult T-cells.

  • 1.

    Adkins B : Neonatal immunology: responses to pathogenic microorganisms and epigenetics reveal an “immunodiverse” developmental state. Immunol. Res. 57, 246–257 (2013)

    • Search Google Scholar
    • Export Citation
  • 2.

    Adkins B , Leclerc C, Marshall-Clarke S: Neonatal adaptive immunity comes of age. Nat. Rev. Immunol. 4, 553–564 (2004)

  • 3.

    Devadas S , Zaritskaya L, Rhee SG, Oberley L, Williams MS: Discrete generation of superoxide and hydrogen peroxide by T cell receptor stimulation: selective regulation of mitogen-activated protein kinase activation and fas ligand expression. J. Exp. Med. 195, 59–70 (2002)

    • Search Google Scholar
    • Export Citation
  • 4.

    Duchen MR : Mitochondria and calcium: from cell signalling to cell death. J. Physiol. 529 Pt 1, 57–68 (2000)

  • 5.

    Elahi S , Ertelt JM, Kinder JM, Jiang TT, Zhang X, Xin L, Chaturvedi V, Strong BS, Qualls JE, Steinbrecher KA, Kalfa TA, Shaaban AF, Way SS: Immunosuppressive CD71+ erythroid cells compromise neonatal host defence against infection. Nature 504, 158–162 (2013)

    • Search Google Scholar
    • Export Citation
  • 6.

    Feske S : Calcium signalling in lymphocyte activation and disease. Nat. Rev. Immunol. 7, 690–702 (2007)

  • 7.

    García Vela JA , Delgado I, Bornstein R, Alvarez B, Auray MC, Martin I, Oña F, Gilsanz F: Comparative intracellular cytokine production by in vitro stimulated T lymphocytes from human umbilical cord blood (HUCB) and adult peripheral blood (APB). Anal. Cell. Pathol. 20, 93–98 (2000)

    • Search Google Scholar
    • Export Citation
  • 8.

    Hogan PG , Lewis RS, Rao A: Molecular basis of calcium signaling in lymphocytes: STIM and ORAI. Annu. Rev. Immunol. 28, 491–533 (2010)

  • 9.

    Hoth M , Button DC, Lewis RS: Mitochondrial control of calcium-channel gating: a mechanism for sustained signaling and transcriptional activation in T lymphocytes. Proc. Natl Acad. Sci. U.S.A. 97, 10607–10612 (2000)

    • Search Google Scholar
    • Export Citation
  • 10.

    Jackson SH , Devadas S, Kwon J, Pinto LA, Williams MS: T cells express a phagocyte-type NADPH oxidase that is activated after T cell receptor stimulation. Nat. Immunol. 5, 818–827 (2004)

    • Search Google Scholar
    • Export Citation
  • 11.

    Jullien P , Cron RQ, Dabbagh K, Cleary A, Chen L, Tran P, Stepick-Biek P, Lewis DB: Decreased CD154 expression by neonatal CD4+ T cells is due to limitations in both proximal and distal events of T cell activation. Int. Immunol. 15, 1461–1472 (2003)

    • Search Google Scholar
    • Export Citation
  • 12.

    Kalyanaraman B , Darley-Usmar V, Davies KJ, Dennery PA, Forman HJ, Grisham MB, Mann GE, Moore K, Roberts LJ, Ischiropoulos H: Measuring reactive oxygen and nitrogen species with fuorescent probes: challenges and limitations. Free Radic. Biol. Med. 52, 1–6 (2012)

    • Search Google Scholar
    • Export Citation
  • 13.

    Kaminski BA , Kadereit S, Miller RE, Leahy P, Stein KR, Topa DA, Radivoyevitch T, Veigl ML, Laughlin MJ: Reduced expression of NFAT-associated genes in UCB versus adult CD4+ T lymphocytes during primary stimulation. Blood 102, 4608–4617 (2003)

    • Search Google Scholar
    • Export Citation
  • 14.

    Kaposi AS , Toldi G, Mészáros G, Szalay B, Veress G, Vásárhelyi B: (2012): Experimental Conditions and Mathematical Analysis of Kinetic Measurements Using Flow Cytometry – The FacsKin Method. In: Flow Cytometry – Recent Perspectives, ed Schmid I, InTech.

    • Search Google Scholar
    • Export Citation
  • 15.

    Kaposi AS , Veress G, Vásárhelyi B, Macardle P, Bailey S, Tulassay T, Treszl A: Cytometry-acquired calcium-fux data analysis in activated lymphocytes. Cytometry A 73, 246–253 (2008)

    • Search Google Scholar
    • Export Citation
  • 16.

    Kilpinen S , Hurme M: Low CD3+CD28-induced interleukin-2 production correlates with decreased reactive oxygen intermediate formation in neonatal T cells. Immunology 94, 167–172 (1998)

    • Search Google Scholar
    • Export Citation
  • 17.

    Mészáros G , Szalay B, Toldi G, Kaposi AS, Vásárhelyi B, Treszl A: Kinetic measurements using fow cytometry: new methods for monitoring intracellular processes. Assay Drug Dev. Technol. 10, 97–104 (2012)

    • Search Google Scholar
    • Export Citation
  • 18.

    Quintana A , Griesemer D, Schwarz EC, Hoth M: Calcium-dependent activation of T-lymphocytes. Pfugers Arch. 450, 1–12 (2005)

  • 19.

    Quintana A , Schwindling C, Wenning AS, Becherer U, Rettig J, Schwarz EC, Hoth M: T cell activation requires mitochondrial translocation to the immunological synapse. Proc. Natl Acad. Sci. U.S.A. 104, 14418–14423 (2007)

    • Search Google Scholar
    • Export Citation
  • 20.

    Rizzuto R , De Stefani D, Raffaello A, Mammucari C: Mitochondria as sensors and regulators of calcium signalling. Nat. Rev. Mol. Cell Biol. 13, 566–578 (2012)

    • Search Google Scholar
    • Export Citation
  • 21.

    Roederer M , Treister A, Moore W, Herzenberg LA: Probability binning comparison: a metric for quantitating univariate distribution differences. Cytometry 45, 37–46 (2001)

    • Search Google Scholar
    • Export Citation
  • 22.

    Sena LA , Li S, Jairaman A, Prakriya M, Ezponda T, Hildeman DA, Wang CR, Schumacker PT, Licht JD, Perlman H, Bryce PJ, Chandel NS: Mitochondria are required for antigen-specifc T cell activation through reactive oxygen species signaling. Immunity 38, 225–236 (2013)

    • Search Google Scholar
    • Export Citation
  • 23.

    Toldi G , Treszl A, Pongor V, Gyarmati B, Tulassay T, Vásárhelyi B: T-lymphocyte calcium infux characteristics and their modulation by Kv1.3 and IKCa1 channel inhibitors in the neonate. Int. Immunol. 22, 769–774 (2010)

    • Search Google Scholar
    • Export Citation
  • 24.

    van der Windt GJ , Everts B, Chang CH, Curtis JD, Freitas TC, Amiel E, Pearce EJ, Pearce EL: Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity 36, 68–78 (2012)

    • Search Google Scholar
    • Export Citation
  • 25.

    Williams MS , Kwon J: T cell receptor stimulation, reactive oxygen species, and cell signaling. Free Radic. Biol. Med. 37, 1144–1151 (2004)

    • Search Google Scholar
    • Export Citation
  • Collapse
  • Expand
Cover Acta Physiologica Hungarica
Acta Physiologica Hungarica
Print ISSN:
0231-424X
Online ISSN:
1588-2683

Senior editors

Editor(s)-in-Chief: Rosivall, László

Honorary Editor(s)-in-Chief): Monos, Emil

Managing Editor(s): Bartha, Jenő; Berhidi, Anna

Co-editor(s): Koller, Ákos; Lénárd, László; Szénási, Gábor

Assistant Editor(s): G. Dörnyei (Budapest), Zs. Miklós (Budapest), Gy. Nádasy (Budapest)

Hungarian Editorial Board

    1. Benedek, György (Szeged)
    1. Benyó, Zoltán (Budapest)
    1. Boros, Mihály (Szeged)
    1. Chernoch, László (Debrecen)
    1. Détári, László (Budapest)
    1. Hamar, János (Budapest)
    1. Hantos, Zoltán (Szeged)
    1. Hunyady, László (Budapest)
    1. Imre, Sándor (Debrecen)
    1. Jancsó, Gábor (Szeged)
    1. Karádi, Zoltán (Pécs)
    1. Kovács, László (Debrecen)
    1. Palkovits, Miklós (Budapest)
    1. Papp, Gyula (Szeged)
    1. Pavlik, Gábor (Budapest)
    1. Spät, András (Budapest)
    1. Szabó, Gyula (Szeged)
    1. Szelényi, Zoltán (Pécs)
    1. Szolcsányi, János (Pécs)
    1. Szollár, Lajos (Budapest)
    1. Szücs, Géza (Debrecen)
    1. Telegdy, Gyula (Szeged)
    1. Toldi, József (Szeged)
    1. Tósaki, Árpád (Debrecen)

International Editorial Board

    1. R. Bauer (Jena)
    1. W. Benjelloun (Rabat)
    1. A. W. Cowley Jr. (Milwaukee)
    1. D. Djuric (Belgrade)
    1. C. Fry (London)
    1. S. Greenwald (London)
    1. O. Hänninen (Kuopio)
    1. H. G. Hinghofer-Szalkay (Graz)
    1. Th. Kenner (Graz)
    1. Gy. Kunos (Richmond)
    1. M. Mahmoudian (Tehran)
    1. T. Mano (Seki, Gifu)
    1. G. Navar (New Orleans)
    1. H. Nishino (Nagoya)
    1. O. Petersen (Liverpool)
    1. U. Pohl (Münich)
    1. R. S. Reneman (Maastricht)
    1. A. Romanovsky (Phoenix)
    1. G. M. Rubanyi (Richmond)
    1. T. Sakata (Oita)
    1. A. Siddiqui (Karachi)
    1. Cs. Szabo (Beverly)
    1. E. Vicaut (Paris)
    1. N. Westerhof (Amsterdam)
    1. L. F. Zhang (Xi'an)

Editorial Office:
Akadémiai Kiadó Zrt.
Prielle Kornélia u. 21–35, H-1117 Budapest, Hungary

Editorial Correspondence:
Acta Physiologica Hungarica
Semmelweis University, Faculty of Medicine Institute of Pathophysiology
Nagyvárad tér 4, H-1089 Budapest, Hungary
Phone/Fax: +36-1-2100-100
E-mail: aph@semmelweis-univ.hu

Indexing and Abstracting Services:

  • Biological Abstracts
  • BIOSIS Previews
  • CAB Abstracts
  • Chemical Abstracts
  • EMBASE/Excerpta Medica
  • Global Health
  • Index Copernicus
  • Index Medicus
  • Medline
  • Referativnyi Zhurnal
  • Science Citation Index Expanded
  • SCOPUS

 

Acta Physiologica Hungarica
Language English
Size  
Year of
Foundation		 1950
Publication
Programme		 changed title
Volumes
per Year		  
Issues
per Year		  
Founder Magyar Tudományos Akadémia
Founder's
Address		 H-1051 Budapest, Hungary, Széchenyi István tér 9.
Publisher Akadémiai Kiadó
Publisher's
Address		 H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Responsible
Publisher		 Chief Executive Officer, Akadémiai Kiadó
ISSN 0231-424X (Print)
ISSN 1588-2683 (Online)

Monthly Content Usage

Abstract Views Full Text Views PDF Downloads
Aug 2024 32 0 0
Sep 2024 26 0 0
Oct 2024 118 0 0
Nov 2024 62 0 0
Dec 2024 17 0 0
Jan 2025 26 0 0
Feb 2025 0 0 0