Authors:
Pedro Milanez-AlmeidaExperimental Immunology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124, Braunschweig, Germany

Search for other papers by Pedro Milanez-Almeida in
Current site
Google Scholar
PubMed
Close
,
Frank KlawonnBioinformatics and Statistics, Helmholtz Centre for Infection Research, Braunschweig, Germany

Search for other papers by Frank Klawonn in
Current site
Google Scholar
PubMed
Close
,
Michael Meyer-HermannSystems Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany

Search for other papers by Michael Meyer-Hermann in
Current site
Google Scholar
PubMed
Close
, and
Jochen HuehnExperimental Immunology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124, Braunschweig, Germany

Search for other papers by Jochen Huehn in
Current site
Google Scholar
PubMed
Close
Restricted access

Abstract

Foxp3+ regulatory T cells (Tregs) hamper efficient immune responses to tumors and chronic infections. Therefore, depletion of Foxp3+ Tregs has been proposed as therapeutic option to boost immune responses and to improve vaccinations. Although Treg-mediated control of T cell homeostasis is well established, Foxp3+ Treg interaction with other immune cell subsets is only incompletely understood. Thus, the present study aimed at examining dynamic effects of experimental Foxp3+ Treg depletion on a broad range of immune cell subsets, including B cells, natural killer cells, and myeloid cells. Striking differences were observed when peripheral lymph nodes (LN) and spleen were compared. B cells, for example, showed a massive and long-lasting accumulation only in LN but not in spleen of transiently Treg-depleted mice. In contrast, monocyte-derived dendritic cells, which are potent inducers of T cell responses, also accumulated selectively, but only transiently in LN, suggesting that this cell population is under very strict control of Foxp3+ Tregs. In summary, the observations described here provide insights into the dynamics of immune cells after selective depletion of Foxp3+ Tregs. This will allow a better prediction of the impact of Treg ablation in translational studies that aim at boosting immune responses and vaccinations.

  • 1. S Sakaguchi 2005 Naturally arising Foxp3-expressing CD25+ CD4+ regulatory T cells in immunological tolerance to self and non-self Nat Immunol 6 345 352.

    • Search Google Scholar
    • Export Citation
  • 2. K Lahl C Loddenkemper C Drouin J Freyer J Arnason G Eberl A Hamann H Wagner J Huehn T Sparwasser 2007 Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease J Exp Med 204 57 63.

    • Search Google Scholar
    • Export Citation
  • 3. JM Kim JP Rasmussen AY Rudensky 2007 Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice Nat Immunol 8 191 197.

    • Search Google Scholar
    • Export Citation
  • 4. K Klages CT Mayer K Lahl C Loddenkemper MW Teng SF Ngiow MJ Smyth A Hamann J Huehn T Sparwasser 2010 Selective depletion of Foxp3+ regulatory T cells improves effective therapeutic vaccination against established melanoma Cancer Res 70 7788 7799.

    • Search Google Scholar
    • Export Citation
  • 5. M Feuerer Y Shen DR Littman C Benoist D Mathis 2009 How punctual ablation of regulatory T cells unleashes an autoimmune lesion within the pancreatic islets Immunity 31 654 664.

    • Search Google Scholar
    • Export Citation
  • 6. B Blankenhaus M Reitz Y Brenz ML Eschbach W Hartmann I Haben T Sparwasser J Huehn A Kuhl TB Feyerabend HR Rodewald M Breloer 2014 Foxp3+ regulatory T cells delay expulsion of intestinal nematodes by suppression of IL-9-driven mast cell activation in BALB/c but not in C57BL/6 mice PLoS Pathog 10 1003913.

    • Search Google Scholar
    • Export Citation
  • 7. Wing K , Sakaguchi S: Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat Immunol 11, 713.

  • 8. K Liu GD Victora TA Schwickert P Guermonprez MM Meredith K Yao FF Chu GJ Randolph AY Rudensky M Nussenzweig 2009 In vivo analysis of dendritic cell development and homeostasis Science 324 392 397.

    • Search Google Scholar
    • Export Citation
  • 9. G Darrasse-Jèze S Deroubaix H Mouquet GD Victora T Eisenreich KH Yao RF Masilamani ML Dustin A Rudensky K Liu MC Nussenzweig 2009 Feedback control of regulatory T cell homeostasis by dendritic cells in vivo J Exp Med 206 1853 1862.

    • Search Google Scholar
    • Export Citation
  • 10. G Gasteiger S Hemmers MA Firth A Le Floc'h M Huse JC Sun AY Rudensky 2013 IL-2-dependent tuning of NK cell sensitivity for target cells is controlled by regulatory T cells J Exp Med 210 1167 1178.

    • Search Google Scholar
    • Export Citation
  • 11. J Sitrin A Ring KC Garcia C Benoist D Mathis 2013 Regulatory T cells control NK cells in an insulitic lesion by depriving them of IL-2 J Exp Med 210 1153 1165.

    • Search Google Scholar
    • Export Citation
  • 12. G Gasteiger S Hemmers PD Bos JC Sun AY Rudensky 2013 IL-2-dependent adaptive control of NK cell homeostasis J Exp Med 210 1179 1187.

    • Search Google Scholar
    • Export Citation
  • 13. J Banchereau F Briere C Caux J Davoust S Lebecque YJ Liu B Pulendran K Palucka 2000 Immunobiology of dendritic cells Annu Rev Immunol 18 767 811.

    • Search Google Scholar
    • Export Citation
  • 14. MK Jenkins A Khoruts E Ingulli DL Mueller SJ McSorley RL Reinhardt A Itano KA Pape 2001 In vivo activation of antigen-specific CD4 T cells Annu Rev Immunol 19 23 45.

    • Search Google Scholar
    • Export Citation
  • 15. MA Cooper TA Fehniger MA Caligiuri 2001 The biology of human natural killer-cell subsets Trends Immunol 22 633 640.

  • 16. I Ludwig-Portugall EE Hamilton-Williams C Gottschalk C Kurts 2008 Cutting edge: CD25+ regulatory T cells prevent expansion and induce apoptosis of B cells specific for tissue autoantigens J Immunol 181 4447 4451.

    • Search Google Scholar
    • Export Citation
  • 17. I Ludwig-Portugall EE Hamilton-Williams J Gotot C Kurts 2009 CD25+ Treg specifically suppress auto-Ab generation against pancreatic tissue autoantigens Eur J Immunol 39 225 233.

    • Search Google Scholar
    • Export Citation
  • 18. HW Lim P Hillsamer AH Banham CH Kim 2005 Cutting edge: direct suppression of B cells by CD4+ CD25+ regulatory T cells J Immunol 175 4180 4183.

    • Search Google Scholar
    • Export Citation
  • 19. HW Lim P Hillsamer CH Kim 2004 Regulatory T cells can migrate to follicles upon T cell activation and suppress GC-Th cells and GC-Th cell-driven B cell responses J Clin Invest 114 1640 1649.

    • Search Google Scholar
    • Export Citation
  • 20. SM Leonardo JA Josephson NL Hartog SB Gauld 2010 Altered B cell development and anergy in the absence of Foxp3 J Immunol 185 2147 2156.

    • Search Google Scholar
    • Export Citation
  • 21. J Riewaldt S Duber M Boernert M Krey M Dembinski S Weiss AI Garbe K Kretschmer 2012 Severe developmental B lymphopoietic defects in Foxp3-deficient mice are refractory to adoptive regulatory t cell therapy Front Immunol 3 1 1.

    • Search Google Scholar
    • Export Citation
  • 22. Y Kerdiles S Ugolini E Vivier 2013 T cell regulation of natural killer cells J Exp Med 210 1065 1068.

  • 23. W Pierson B Cauwe A Policheni SM Schlenner D Franckaert J Berges S Humblet-Baron S Schönefeldt MJ Herold D Hildeman A Strasser P Bouillet LF Lu P Matthys AA Freitas RJ Luther CT Weaver J Dooley DH Gray A Liston 2013 Antiapoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3+ regulatory T cells Nat Immunol 14 959 965.

    • Search Google Scholar
    • Export Citation
  • 24. J Suffner K Hochweller MC Kühnle X Li RA Kroczek N Garbi GJ Hämmerling 2010 Dendritic cells support homeostatic expansion of Foxp3+ regulatory T cells in Foxp3.LuciDTR mice J Immunol 184 1810 1820.

    • Search Google Scholar
    • Export Citation
  • 25. GT Belz SL Nutt 2012 Transcriptional programming of the dendritic cell network Nat Rev Immunol 12 101 113.

  • 26. SJ Seo ML Fields JL Buckler AJ Reed L Mandik-Nayak SA Nish RJ Noelle LA Turka FD Finkelman AJ Caton J Erikson 2002 The impact of T helper and T regulatory cells on the regulation of anti-double-stranded DNA B cells Immunity 16 535 546.

    • Search Google Scholar
    • Export Citation
  • 27. MA Cooper TA Fehniger A Fuchs M Colonna MA Caligiuri 2004 NK cell and DC interactions Trends Immunol 25 47 52.

  • 28. A Marcais S Viel M Grau T Henry J Marvel T Walzer 2013 Regulation of mouse NK cell development and function by cytokines Front Immunol 4 4 0.

    • Search Google Scholar
    • Export Citation
  • 29. M Terme N Chaput B Combadiere A Ma T Ohteki L Zitvogel 2008 Regulatory T cells control dendritic cell/NK cell cross-talk in lymph nodes at the steady state by inhibiting CD4+ self-reactive T cells J Immunol 180 4679 4686.

    • Search Google Scholar
    • Export Citation
  • 30. V Bronte P Zanovello 2005 Regulation of immune responses by L-arginine metabolism Nat Rev Immunol 5 641 654.

  • 31. DI Gabrilovich S Nagaraj 2009 Myeloid-derived suppressor cells as regulators of the immune system Nat Rev Immunol 9 162 174.

  • 32. JI Youn S Nagaraj M Collazo DI Gabrilovich 2008 Subsets of myeloid-derived suppressor cells in tumor-bearing mice J Immunol 181 5791 5802.

    • Search Google Scholar
    • Export Citation
  • 33. Y Sawanobori S Ueha M Kurachi T Shimaoka JE Talmadge J Abe Y Shono M Kitabatake K Kakimi N Mukaida K Matsushima 2008 Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice Blood 111 5457 5466.

    • Search Google Scholar
    • Export Citation
  • 34. K Movahedi M Guilliams J Van den Bossche R Van den Bergh C Gysemans A Beschin P De Baetselier JA Van Ginderachter 2008 Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity Blood 111 4233 4244.

    • Search Google Scholar
    • Export Citation
  • 35. AM Lesokhin TM Hohl S Kitano C Cortez D Hirschhorn-Cymerman F Avogadri GA Rizzuto JJ Lazarus EG Pamer AN Houghton T Merghoub JD Wolchok 2012 Monocytic CCR2+ myeloid-derived suppressor cells promote immune escape by limiting activated CD8 T-cell infiltration into the tumor microenvironment Cancer Res 72 876 886.

    • Search Google Scholar
    • Export Citation
  • 36. C Peter S Wesselborg M Herrmann K Lauber 2010 Dangerous attraction: phagocyte recruitment and danger signals of apoptotic and necrotic cells Apoptosis 15 1007 1028.

    • Search Google Scholar
    • Export Citation
  • 37. RE Mebius G Kraal 2005 Structure and function of the spleen Nat Rev Immunol 5 606 616.

  • 38. C Cheong I Matos JH Choi DB Dandamudi E Shrestha MP Longhi KL Jeffrey RM Anthony C Kluger G Nchinda H Koh A Rodriguez J Idoyaga M Pack K Velinzon CG Park RM Steinman 2010 Microbial stimulation fully differentiates monocytes to DC-SIGN/CD209+ dendritic cells for immune T cell areas Cell 143 416 429.

    • Search Google Scholar
    • Export Citation
  • 39. CG Lo TT Lu JG Cyster 2003 Integrin-dependence of lymphocyte entry into the splenic white pulp J Exp Med 197 353 361.

  • 40. JP Girard C Moussion R Forster 2012 HEVs, lymphatics and homeostatic immune cell trafficking in lymph nodes Nat Rev Immunol 12 762 773.

    • Search Google Scholar
    • Export Citation
  • 41. RM Thomas H Sai AD Wells 2012 Conserved intergenic elements and DNA methylation cooperate to regulate transcription at the il17 locus J Biol Chem 287 25049 25059.

    • Search Google Scholar
    • Export Citation
  • 42. JP Hindley E Jones K Smart H Bridgeman SN Lauder B Ondondo S Cutting K Ladell KK Wynn D Withers DA Price A Ager AJ Godkin AM Gallimore 2012 T-cell trafficking facilitated by high endothelial venules is required for tumor control after regulatory T-cell depletion Cancer Res 72 5473 5482.

    • Search Google Scholar
    • Export Citation
  • Collapse
  • Expand
The author instruction is available in PDF.
Please, download the file from HERE.
 

Senior editors

Editor(s)-in-Chief: Dunay, Ildiko Rita

Editor(s)-in-Chief: Heimesaat, Markus M.

Vice Editor(s)-in-Chief: Fuchs, Anja

Editorial Board

Chair of the Editorial Board:
Jeffrey S. Buguliskis (Thomas Jefferson University, USA)

  • Jörn Albring (University of Münster, Germany)
  • Stefan Bereswill (Charité - University Medicine Berlin, Germany)
  • Dunja Bruder (University of Megdeburg, Germany)
  • Jan Buer (University of Duisburg, Germany)
  • Jeff Buguliskis (Thomas Jefferson University, USA)
  • Edit Buzas (Semmelweis University, Hungary)
  • Charles Collyer (University of Sydney, Australia)
  • Renato Damatta (UENF, Brazil)
  • Ivelina Damjanova (Semmelweis University, Hungary)
  • Maria Deli (Biological Research Center, HAS, Hungary)
  • Olgica Djurković-Djaković (University of Belgrade, Serbia)
  • Jean-Dennis Docquier (University of Siena, Italy)
  • Anna Erdei (Eötvös Loránd University, Hungary)
  • Zsuzsanna Fabry (University of Washington, USA)
  • Beniam Ghebremedhin (Witten/Herdecke University, Germany)
  • Nancy Guillen (Institute Pasteur, France)
  • Georgina L. Hold (University of Aberdeen, United Kingdom)
  • Ralf Ignatius (Charité - University Medicine Berlin, Germany)
  • Zsuzsanna Izsvak (MDC-Berlin, Germany)
  • Achim Kaasch (University of Cologne, Germany)
  • Tamás Laskay (University of Lübeck, Germany)
  • Oliver Liesenfeld (Roche, USA)
  • Shreemanta Parida (Vaccine Grand Challenge Program, India)
  • Matyas Sandor (University of Wisconsin, USA)
  • Ulrich Steinhoff (University of Marburg, Germany)
  • Michal Toborek (University of Miami, USA)
  • Mary Jo Wick (University of Gothenburg, Sweden)
  • Susanne A. Wolf (MDC-Berlin, Germany)

 

Dr. Dunay, Ildiko Rita
Magdeburg, Germany
E-mail: ildikodunay@gmail.com

Indexing and Abstracting Services:

  • PubMed Central
  • Scopus
  • ESCI
  • CABI

 

2021  
Web of Science  
Total Cites
WoS
790
Journal Impact Factor not applicable
Rank by Impact Factor not applicable
Impact Factor
without
Journal Self Cites
not applicable
5 Year
Impact Factor
not applicable
Journal Citation Indicator 0,64
Rank by Journal Citation Indicator Microbiology 81/157
Scimago  
Scimago
H-index
not indexed
Scimago
Journal Rank
not indexed
Scimago Quartile Score not indexed
Scopus  
Scopus
Cite Score
not indexed
Scopus
CIte Score Rank
  not indexed
Scopus
SNIP
not indexed

2020  
CrossRef Documents 23
WoS Cites 708
Wos H-index 27
Days from submission to acceptance 219
Days from acceptance to publication 176
Acceptance Rate 70%

2019  
WoS
Cites
558
CrossRef
Documents
24
Acceptance
Rate
92%

 

European Journal of Microbiology and Immunology
Publication Model Gold Open Access
Submission Fee none
Article Processing Charge 600 EUR/article
Regional discounts on country of the funding agency World Bank Lower-middle-income economies: 50%
World Bank Low-income economies: 100%
Further Discounts Editorial Board / Advisory Board members: 50%
Corresponding authors, affiliated to an EISZ member institution subscribing to the journal package of Akadémiai Kiadó: 100%
Subscription Information Gold Open Access
Purchase per Title  

European Journal of Microbiology and Immunology
Language English
Size A4
Year of
Foundation
2011
Volumes
per Year
1
Issues
per Year
4
Founder Akadémiai Kiadó
Founder's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Publisher Akadémiai Kiadó
Publisher's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Responsible
Publisher
Chief Executive Officer, Akadémiai Kiadó
ISSN 2062-509X (Print)
ISSN 2062-8633 (Online)

Monthly Content Usage

Abstract Views Full Text Views PDF Downloads
Jun 2022 1 0 0
Jul 2022 4 0 0
Aug 2022 13 0 0
Sep 2022 0 0 0
Oct 2022 2 0 0
Nov 2022 7 0 0
Dec 2022 0 0 0