Shared and Unique Features Distinguishing Follicular T Helper and Regulatory Cells of Peripheral Lymph Node and Peyer’s Patches
Abstract
Follicular helper (TFH) and regulatory (TFR) cells are essential players in managing germinal center (GC) reactions that accomplish effective humoral immune responses. Transcriptome analyses were done comparing gene regulation of TFH and TFR cells isolated from Peyer’s Patches (PP) and immunized peripheral lymph nodes (pLNs) revealing many regulatory patterns common to all follicular cells. Yet, in contrast to TFH cells, the upregulation or downregulation of many genes was attenuated substantially in pLN TFR cells when compared to those of PP. Additionally, PP but not pLN TFR cells were largely unresponsive to IL2 and expressed Il4 as well as Il21. Together with fundamental differences in gene expression that were found between cells of both compartments this emphasizes specific adaptations of follicular T cell functions to their micro-milieu. Furthermore, although GL7 expression distinguishes matured follicular T cells, GL7+ as well as GL7– cells are present in the GC.
- Authors:
- Publication Date:
- Research Org.:
- Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
- Sponsoring Org.:
- USDOE National Nuclear Security Administration (NNSA)
- OSTI Identifier:
- 1432391
- Alternate Identifier(s):
- OSTI ID: 1527289
- Report Number(s):
- LLNL-JRNL-741132
Journal ID: ISSN 1664-3224; 714
- Grant/Contract Number:
- AC52-07NA27344
- Resource Type:
- Published Article
- Journal Name:
- Frontiers in Immunology
- Additional Journal Information:
- Journal Name: Frontiers in Immunology Journal Volume: 9; Journal ID: ISSN 1664-3224
- Publisher:
- Frontiers Media SA
- Country of Publication:
- Switzerland
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Georgiev, Hristo, Ravens, Inga, Papadogianni, Georgia, Halle, Stephan, Malissen, Bernard, Loots, Gabriela G., Förster, Reinhold, and Bernhardt, Günter. Shared and Unique Features Distinguishing Follicular T Helper and Regulatory Cells of Peripheral Lymph Node and Peyer’s Patches. Switzerland: N. p., 2018.
Web. doi:10.3389/fimmu.2018.00714.
Georgiev, Hristo, Ravens, Inga, Papadogianni, Georgia, Halle, Stephan, Malissen, Bernard, Loots, Gabriela G., Förster, Reinhold, & Bernhardt, Günter. Shared and Unique Features Distinguishing Follicular T Helper and Regulatory Cells of Peripheral Lymph Node and Peyer’s Patches. Switzerland. https://doi.org/10.3389/fimmu.2018.00714
Georgiev, Hristo, Ravens, Inga, Papadogianni, Georgia, Halle, Stephan, Malissen, Bernard, Loots, Gabriela G., Förster, Reinhold, and Bernhardt, Günter. Mon .
"Shared and Unique Features Distinguishing Follicular T Helper and Regulatory Cells of Peripheral Lymph Node and Peyer’s Patches". Switzerland. https://doi.org/10.3389/fimmu.2018.00714.
@article{osti_1432391,
title = {Shared and Unique Features Distinguishing Follicular T Helper and Regulatory Cells of Peripheral Lymph Node and Peyer’s Patches},
author = {Georgiev, Hristo and Ravens, Inga and Papadogianni, Georgia and Halle, Stephan and Malissen, Bernard and Loots, Gabriela G. and Förster, Reinhold and Bernhardt, Günter},
abstractNote = {Follicular helper (TFH) and regulatory (TFR) cells are essential players in managing germinal center (GC) reactions that accomplish effective humoral immune responses. Transcriptome analyses were done comparing gene regulation of TFH and TFR cells isolated from Peyer’s Patches (PP) and immunized peripheral lymph nodes (pLNs) revealing many regulatory patterns common to all follicular cells. Yet, in contrast to TFH cells, the upregulation or downregulation of many genes was attenuated substantially in pLN TFR cells when compared to those of PP. Additionally, PP but not pLN TFR cells were largely unresponsive to IL2 and expressed Il4 as well as Il21. Together with fundamental differences in gene expression that were found between cells of both compartments this emphasizes specific adaptations of follicular T cell functions to their micro-milieu. Furthermore, although GL7 expression distinguishes matured follicular T cells, GL7+ as well as GL7– cells are present in the GC.},
doi = {10.3389/fimmu.2018.00714},
journal = {Frontiers in Immunology},
number = ,
volume = 9,
place = {Switzerland},
year = {2018},
month = {4}
}
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.3389/fimmu.2018.00714
https://doi.org/10.3389/fimmu.2018.00714
Other availability
Search WorldCat to find libraries that may hold this journal
Cited by: 3 works
Citation information provided by
Web of Science
Web of Science
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
A distinct subpopulation of CD25 − T-follicular regulatory cells localizes in the germinal centers
journal, July 2017
- Wing, James Badger; Kitagawa, Yohko; Locci, Michela
- Proceedings of the National Academy of Sciences, Vol. 114, Issue 31
CCAAT/Enhancer-binding Protein α (C/EBPα) Is Critical for Interleukin-4 Expression in Response to FcϵRI Receptor Cross-linking
journal, March 2011
- Qi, Xiaopeng; Nishida, Jun; Chaves, Lee
- Journal of Biological Chemistry, Vol. 286, Issue 18
How T Cells Earn the Follicular Rite of Passage
journal, November 2011
- Vinuesa, Carola G.; Cyster, Jason G.
- Immunity, Vol. 35, Issue 5
Foxp3+ T Cells Regulate Immunoglobulin A Selection and Facilitate Diversification of Bacterial Species Responsible for Immune Homeostasis
journal, July 2014
- Kawamoto, Shimpei; Maruya, Mikako; Kato, Lucia M.
- Immunity, Vol. 41, Issue 1
Suppression by TFR cells leads to durable and selective inhibition of B cell effector function
journal, October 2016
- Sage, Peter T.; Ron-Harel, Noga; Juneja, Vikram R.
- Nature Immunology, Vol. 17, Issue 12
Transcription factor achaete-scute homologue 2 initiates follicular T-helper-cell development
journal, January 2014
- Liu, Xindong; Chen, Xin; Zhong, Bo
- Nature, Vol. 507, Issue 7493
Bach2–Batf interactions control Th2-type immune response by regulating the IL-4 amplification loop
journal, September 2016
- Kuwahara, Makoto; Ise, Wataru; Ochi, Mizuki
- Nature Communications, Vol. 7, Issue 1
A Fundamental Role for Interleukin-21 in the Generation of T Follicular Helper Cells
journal, July 2008
- Vogelzang, Alexis; McGuire, Helen M.; Yu, Di
- Immunity, Vol. 29, Issue 1
T follicular helper and T follicular regulatory cells have different TCR specificity
journal, April 2017
- Maceiras, Ana Raquel; Almeida, Silvia Cristina Paiva; Mariotti-Ferrandiz, Encarnita
- Nature Communications, Vol. 8, Issue 1
SATB1 Expression Governs Epigenetic Repression of PD-1 in Tumor-Reactive T Cells
journal, January 2017
- Stephen, Tom L.; Payne, Kyle K.; Chaurio, Ricardo A.
- Immunity, Vol. 46, Issue 1
T Follicular Helper Cell Differentiation, Function, and Roles in Disease
journal, October 2014
- Crotty, Shane
- Immunity, Vol. 41, Issue 4
Th2 Lymphoproliferative Disorder of Lat Y136F Mutant Mice Unfolds Independently of TCR-MHC Engagement and Is Insensitive to the Action of Foxp3 + Regulatory T Cells
journal, January 2008
- Wang, Ying; Kissenpfennig, Adrien; Mingueneau, Michael
- The Journal of Immunology, Vol. 180, Issue 3
Gadd45β is important for perpetuating cognate and inflammatory signals in T cells
journal, December 2003
- Lu, Binfeng; Ferrandino, Anthony F.; Flavell, Richard A.
- Nature Immunology, Vol. 5, Issue 1
Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions
journal, July 2011
- Chung, Yeonseok; Tanaka, Shinya; Chu, Fuliang
- Nature Medicine, Vol. 17, Issue 8
ICOS Deficiency Is Associated with a Severe Reduction of CXCR5 + CD4 Germinal Center Th Cells
journal, September 2006
- Bossaller, Lukas; Burger, Jan; Draeger, Ruth
- The Journal of Immunology, Vol. 177, Issue 7
GILZ regulates Th17 responses and restrains IL-17-mediated skin inflammation
journal, July 2015
- Jones, Sarah A.; Perera, Diluptha N.; Fan, Huapeng
- Journal of Autoimmunity, Vol. 61
T-cell subsets in the germinal center
journal, February 2013
- Ramiscal, Roybel R.; Vinuesa, Carola G.
- Immunological Reviews, Vol. 252, Issue 1
Foxp3+ follicular regulatory T cells control the germinal center response
journal, July 2011
- Linterman, Michelle A.; Pierson, Wim; Lee, Sau K.
- Nature Medicine, Vol. 17, Issue 8
Functional and Structural Insights into ASB2α, a Novel Regulator of Integrin-dependent Adhesion of Hematopoietic Cells
journal, July 2011
- Lamsoul, Isabelle; Burande, Clara F.; Razinia, Ziba
- Journal of Biological Chemistry, Vol. 286, Issue 35
Cytokine-secreting follicular T cells shape the antibody repertoire
journal, March 2009
- Reinhardt, R. Lee; Liang, Hong-Erh; Locksley, Richard M.
- Nature Immunology, Vol. 10, Issue 4
Homeostatic chemokines in development, plasticity, and functional organization of the intestinal immune system
journal, June 2008
- Förster, Reinhold; Pabst, Oliver; Bernhardt, Günter
- Seminars in Immunology, Vol. 20, Issue 3
T Follicular Helper Cell Dynamics in Germinal Centers
journal, July 2013
- Shulman, Z.; Gitlin, A. D.; Targ, S.
- Science, Vol. 341, Issue 6146
The receptor PD-1 controls follicular regulatory T cells in the lymph nodes and blood
journal, December 2012
- Sage, Peter T.; Francisco, Loise M.; Carman, Christopher V.
- Nature Immunology, Vol. 14, Issue 2
Dynamic control of 1 integrin adhesion by the plexinD1-sema3E axis
journal, December 2013
- Choi, Y. I.; Duke-Cohan, J. S.; Chen, W.
- Proceedings of the National Academy of Sciences, Vol. 111, Issue 1
The Interleukin-2-mTORc1 Kinase Axis Defines the Signaling, Differentiation, and Metabolism of T Helper 1 and Follicular B Helper T Cells
journal, October 2015
- Ray, John P.; Staron, Matthew M.; Shyer, Justin A.
- Immunity, Vol. 43, Issue 4
Interleukin-4 Production by Follicular Helper T Cells Requires the Conserved Il4 Enhancer Hypersensitivity Site V
journal, February 2012
- Vijayanand, Pandurangan; Seumois, Grégory; Simpson, Laura J.
- Immunity, Vol. 36, Issue 2
Circulating T follicular regulatory and helper cells have memory-like properties
journal, October 2014
- Sage, Peter T.; Alvarez, David; Godec, Jernej
- Journal of Clinical Investigation, Vol. 124, Issue 12
The Transcription Factor KLF2 Restrains CD4 + T Follicular Helper Cell Differentiation
journal, February 2015
- Lee, June-Yong; Skon, Cara N.; Lee, You Jeong
- Immunity, Vol. 42, Issue 2
IL-21 restricts T follicular regulatory T cell proliferation through Bcl-6 mediated inhibition of responsiveness to IL-2
journal, March 2017
- Jandl, Christoph; Liu, Sue M.; Cañete, Pablo F.
- Nature Communications, Vol. 8, Issue 1
Hemophagocytic lymphohistiocytosis in syntaxin-11–deficient mice: T-cell exhaustion limits fatal disease
journal, January 2013
- Kögl, Tamara; Müller, Jürgen; Jessen, Birthe
- Blood, Vol. 121, Issue 4
Germinal Center T Follicular Helper Cell IL-4 Production Is Dependent on Signaling Lymphocytic Activation Molecule Receptor (CD150)
journal, June 2010
- Yusuf, Isharat; Kageyama, Robin; Monticelli, Laurel
- The Journal of Immunology, Vol. 185, Issue 1
GARP (LRRC32) is essential for the surface expression of latent TGF- on platelets and activated FOXP3+ regulatory T cells
journal, July 2009
- Tran, D. Q.; Andersson, J.; Wang, R.
- Proceedings of the National Academy of Sciences, Vol. 106, Issue 32
Lymphoid reservoirs of antigen-specific memory T helper cells
journal, May 2007
- Fazilleau, Nicolas; Eisenbraun, Michael D.; Malherbe, Laurent
- Nature Immunology, Vol. 8, Issue 7
The Transcriptional Repressor Bcl-6 Directs T Follicular Helper Cell Lineage Commitment
journal, September 2009
- Yu, Di; Rao, Sudha; Tsai, Louis M.
- Immunity, Vol. 31, Issue 3
IL-27 supports germinal center function by enhancing IL-21 production and the function of T follicular helper cells
journal, November 2010
- Batten, Marcel; Ramamoorthi, Nandhini; Kljavin, Noelyn M.
- The Journal of Experimental Medicine, Vol. 207, Issue 13
The small MAF transcription factors MAFF, MAFG and MAFK: Current knowledge and perspectives
journal, October 2012
- Kannan, Meenakshi B.; Solovieva, Vera; Blank, Volker
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Vol. 1823, Issue 10
Germinal Center B Cell and T Follicular Helper Cell Development Initiates in the Interfollicular Zone
journal, June 2011
- Kerfoot, Steven M.; Yaari, Gur; Patel, Jaymin R.
- Immunity, Vol. 34, Issue 6
TFH cells progressively differentiate to regulate the germinal center response
journal, August 2016
- Weinstein, Jason S.; Herman, Edward I.; Lainez, Begoña
- Nature Immunology, Vol. 17, Issue 10
Metabolic checkpoints in activated T cells
journal, September 2012
- Wang, Ruoning; Green, Douglas R.
- Nature Immunology, Vol. 13, Issue 10
Critical Regulation of Early Th17 Cell Differentiation by Interleukin-1 Signaling
journal, April 2009
- Chung, Yeonseok; Chang, Seon Hee; Martinez, Gustavo J.
- Immunity, Vol. 30, Issue 4
Bcl-6 directly represses the gene program of the glycolysis pathway
journal, September 2014
- Oestreich, Kenneth J.; Read, Kaitlin A.; Gilbertson, Sarah E.
- Nature Immunology, Vol. 15, Issue 10
Batf is important for IL-4 expression in T follicular helper cells
journal, August 2015
- Sahoo, Anupama; Alekseev, Andrei; Tanaka, Kentaro
- Nature Communications, Vol. 6, Issue 1
Unequal Death in T Helper Cell (Th)1 and Th2 Effectors: Th1, but not Th2, Effectors Undergo Rapid Fas/FasL-mediated Apoptosis
journal, May 1997
- Zhang, Xiaohong; Brunner, Thomas; Carter, Laura
- The Journal of Experimental Medicine, Vol. 185, Issue 10
Posttranscriptional Control of T Cell Effector Function by Aerobic Glycolysis
journal, June 2013
- Chang, Chih-Hao; Curtis, Jonathan D.; Maggi, Leonard B.
- Cell, Vol. 153, Issue 6
The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells
journal, December 2008
- Bauquet, Aurelie T.; Jin, Hulin; Paterson, Alison M.
- Nature Immunology, Vol. 10, Issue 2
Follicular B helper T cell activity is confined to CXCR5hiICOShi CD4 T cells and is independent of CD57 expression
journal, July 2006
- Rasheed, Ata-Ur; Rahn, Hans-Peter; Sallusto, Federica
- European Journal of Immunology, Vol. 36, Issue 7
The development and fate of follicular helper T cells defined by an IL-21 reporter mouse
journal, April 2012
- Lüthje, Katja; Kallies, Axel; Shimohakamada, Yoko
- Nature Immunology, Vol. 13, Issue 5
T follicular regulatory cells
journal, April 2016
- Sage, Peter T.; Sharpe, Arlene H.
- Immunological Reviews, Vol. 271, Issue 1
Bcl6 and Blimp-1 Are Reciprocal and Antagonistic Regulators of T Follicular Helper Cell Differentiation
journal, July 2009
- Johnston, R. J.; Poholek, A. C.; DiToro, D.
- Science, Vol. 325, Issue 5943
Role of CXCR5 and CCR7 in Follicular Th Cell Positioning and Appearance of a Programmed Cell Death Gene-1 High Germinal Center-Associated Subpopulation
journal, October 2007
- Haynes, Nicole M.; Allen, Christopher D. C.; Lesley, Robin
- The Journal of Immunology, Vol. 179, Issue 8
Interleukin-2 Inhibits Germinal Center Formation by Limiting T Follicular Helper Cell Differentiation
journal, May 2012
- Ballesteros-Tato, André; León, Beatriz; Graf, Beth A.
- Immunity, Vol. 36, Issue 5
Dynamic regulation of T follicular regulatory cell responses by interleukin 2 during influenza infection
journal, September 2017
- Botta, Davide; Fuller, Michael J.; Marquez-Lago, Tatiana T.
- Nature Immunology, Vol. 18, Issue 11
Molecular and cellular insights into T cell exhaustion
journal, July 2015
- Wherry, E. John; Kurachi, Makoto
- Nature Reviews Immunology, Vol. 15, Issue 8
Follicular B Helper T Cells Express Cxc Chemokine Receptor 5, Localize to B Cell Follicles, and Support Immunoglobulin Production
journal, November 2000
- Breitfeld, Dagmar; Ohl, Lars; Kremmer, Elisabeth
- The Journal of Experimental Medicine, Vol. 192, Issue 11
Identification of a secreted BMP antagonist, ectodin, integrating BMP, FGF, and SHH signals from the tooth enamel knot
journal, December 2003
- Laurikkala, Johanna; Kassai, Yoshiaki; Pakkasjärvi, Leila
- Developmental Biology, Vol. 264, Issue 1
Plasticity of TH17 cells in Peyer's patches is responsible for the induction of T cell–dependent IgA responses
journal, March 2013
- Hirota, Keiji; Turner, Jan-Eric; Villa, Matteo
- Nature Immunology, Vol. 14, Issue 4
Ephrin B1–mediated repulsion and signaling control germinal center T cell territoriality and function
journal, April 2017
- Lu, Peiwen; Shih, Changming; Qi, Hai
- Science, Vol. 356, Issue 6339
Bone morphogenetic proteins inhibit CD40L/IL-21-induced Ig production in human Bcells: Differential effects of BMP-6 and BMP-7
journal, October 2011
- Huse, Kanutte; Bakkebø, Maren; Oksvold, Morten P.
- European Journal of Immunology, Vol. 41, Issue 11
The transcription factor BATF controls the global regulators of class-switch recombination in both B cells and T cells
journal, May 2011
- Ise, Wataru; Kohyama, Masako; Schraml, Barbara U.
- Nature Immunology, Vol. 12, Issue 6
Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2
journal, May 2012
- Yokosuka, Tadashi; Takamatsu, Masako; Kobayashi-Imanishi, Wakana
- The Journal of Experimental Medicine, Vol. 209, Issue 6
IL-17RA Is Essential for Optimal Localization of Follicular Th Cells in the Germinal Center Light Zone To Promote Autoantibody-Producing B Cells
journal, July 2013
- Ding, Yanna; Li, Jun; Wu, Qi
- The Journal of Immunology, Vol. 191, Issue 4
A Temporal Switch in the Germinal Center Determines Differential Output of Memory B and Plasma Cells
journal, January 2016
- Weisel, Florian J.; Zuccarino-Catania, Griselda V.; Chikina, Maria
- Immunity, Vol. 44, Issue 1
Preferential Generation of Follicular B Helper T Cells from Foxp3+ T Cells in Gut Peyer's Patches
journal, March 2009
- Tsuji, M.; Komatsu, N.; Kawamoto, S.
- Science, Vol. 323, Issue 5920
PSGL-1 function in immunity and steady state homeostasis
journal, July 2009
- Carlow, Douglas A.; Gossens, Klaus; Naus, Silvia
- Immunological Reviews, Vol. 230, Issue 1
Peyer's patches: organizing B-cell responses at the intestinal frontier
journal, April 2016
- Reboldi, Andrea; Cyster, Jason G.
- Immunological Reviews, Vol. 271, Issue 1
The impact of cell-bound antigen transport on mucosal tolerance induction
journal, June 2007
- Pabst, Oliver; Bernhardt, Günter; Förster, Reinhold
- Journal of Leukocyte Biology, Vol. 82, Issue 4
The 3′ Enhancer CNS2 Is a Critical Regulator of Interleukin-4-Mediated Humoral Immunity in Follicular Helper T Cells
journal, February 2012
- Harada, Yohsuke; Tanaka, Shinya; Motomura, Yasutaka
- Immunity, Vol. 36, Issue 2
IgA production requires B cell interaction with subepithelial dendritic cells in Peyers patches
journal, May 2016
- Reboldi, A.; Arnon, T. I.; Rodda, L. B.
- Science, Vol. 352, Issue 6287
Regulated Compartmentalization of Programmed Cell Death-1 Discriminates CD4 + CD25 + Resting Regulatory T Cells from Activated T Cells
journal, February 2006
- Raimondi, Giorgio; Shufesky, William J.; Tokita, Daisuke
- The Journal of Immunology, Vol. 176, Issue 5
Foxp3-dependent programme of regulatory T-cell differentiation
journal, January 2007
- Gavin, Marc A.; Rasmussen, Jeffrey P.; Fontenot, Jason D.
- Nature, Vol. 445, Issue 7129
Works referencing / citing this record:
Regulation of the Germinal Center Response
journal, October 2018
- Stebegg, Marisa; Kumar, Saumya D.; Silva-Cayetano, Alyssa
- Frontiers in Immunology, Vol. 9
T-Follicular Regulatory Cells: Potential Therapeutic Targets in Rheumatoid Arthritis
journal, November 2019
- Ding, Tingting; Niu, Hongqing; Zhao, Xiangcong
- Frontiers in Immunology, Vol. 10
T-Follicular Regulatory Cells: Potential Therapeutic Targets in Rheumatoid Arthritis
journal, November 2019
- Ding, Tingting; Niu, Hongqing; Zhao, Xiangcong
- Frontiers in Immunology, Vol. 10
Regulation of the Germinal Center Response
journal, October 2018
- Stebegg, Marisa; Kumar, Saumya D.; Silva-Cayetano, Alyssa
- Frontiers in Immunology, Vol. 9
Wnt Antagonists in Hematopoietic and Immune Cell Fate: Implications for Osteoporosis Therapies
journal, March 2019
- Chicana, Betsabel; Donham, Cristine; Millan, Alberto J.
- Current Osteoporosis Reports, Vol. 17, Issue 2