Journal Article
. 2015 Jan; 194(5):2148-59.
doi: 10.4049/jimmunol.1401876.

A transendocytosis model of CTLA-4 function predicts its suppressive behavior on regulatory T cells

Tie Zheng Hou 1 Omar S Qureshi 2 Chun Jing Wang 1 Jennifer Baker 2 Stephen P Young 2 Lucy S K Walker 1 David M Sansom 3 
Affiliations
  • PMID: 25632005
  •     52 References
  •     44 citations

Abstract

Manipulation of the CD28/CTLA-4 pathway is at the heart of a number of immunomodulatory approaches used in both autoimmunity and cancer. Although it is clear that CTLA-4 is a critical regulator of T cell responses, the immunological contexts in which CTLA-4 controls immune responses are not well defined. In this study, we show that whereas CD80/CD86-dependent activation of resting human T cells caused extensive T cell proliferation and robust CTLA-4 expression, in this context CTLA-4 blocking Abs had no impact on the response. In contrast, in settings where CTLA-4(+) cells were present as "regulators," inhibition of resting T cell responses was dependent on CTLA-4 expression and specifically related to the number of APC. At low numbers of APC or low levels of ligand, CTLA-4-dependent suppression was highly effective whereas at higher APC numbers or high levels of ligand, inhibition was lost. Accordingly, the degree of suppression correlated with the level of CD86 expression remaining on the APC. These data reveal clear rules for the inhibitory function of CTLA-4 on regulatory T cells, which are predicted by its ability to remove ligands from APC.

Structural analysis of CTLA-4 function in vivo.
E L Masteller, E Chuang, +2 authors, C B Thompson.
J Immunol, 2000 May 09; 164(10). PMID: 10799894
The reverse stop-signal model for CTLA4 function.
Christopher E Rudd.
Nat Rev Immunol, 2008 Jan 26; 8(2). PMID: 18219311
Review.
CD4+CD25+ regulatory T cells down-regulate co-stimulatory molecules on antigen-presenting cells.
L Cederbom, H Hall, F Ivars.
Eur J Immunol, 2000 Jul 18; 30(6). PMID: 10898488
Highly Cited.
Dendritic cells as sensors of infection.
C Reis e Sousa.
Immunity, 2001 May 24; 14(5). PMID: 11371351
Review.
Toll-like receptors: critical proteins linking innate and acquired immunity.
S Akira, K Takeda, T Kaisho.
Nat Immunol, 2001 Jul 31; 2(8). PMID: 11477402
Highly Cited. Review.
CD4+CD28- costimulation-independent T cells in multiple sclerosis.
S Markovic-Plese, I Cortese, +2 authors, R Martin.
J Clin Invest, 2001 Oct 17; 108(8). PMID: 11602626    Free PMC article.
CTLA-4 differentially regulates T cell responses to endogenous tissue protein versus exogenous immunogen.
Lucy S K Walker, Lara J Ausubel, +2 authors, Abul K Abbas.
J Immunol, 2002 Nov 22; 169(11). PMID: 12444125
An autoimmune disease-associated CTLA-4 splice variant lacking the B7 binding domain signals negatively in T cells.
Lalitha Vijayakrishnan, Jacqueline M Slavik, +9 authors, Vijay K Kuchroo.
Immunity, 2004 May 15; 20(5). PMID: 15142525
T-cell antigen CD28 mediates adhesion with B cells by interacting with activation antigen B7/BB-1.
P S Linsley, E A Clark, J A Ledbetter.
Proc Natl Acad Sci U S A, 1990 Jul 01; 87(13). PMID: 2164219    Free PMC article.
Highly Cited.
Binding of the B cell activation antigen B7 to CD28 costimulates T cell proliferation and interleukin 2 mRNA accumulation.
P S Linsley, W Brady, +3 authors, J A Ledbetter.
J Exp Med, 1991 Mar 01; 173(3). PMID: 1847722    Free PMC article.
Highly Cited.
B70 antigen is a second ligand for CTLA-4 and CD28.
M Azuma, D Ito, +4 authors, C Somoza.
Nature, 1993 Nov 04; 366(6450). PMID: 7694153
Highly Cited.
B7/CD28 but not LFA-3/CD2 interactions can provide 'third-party' co-stimulation for human T-cell activation.
D M Sansom, A Wilson, +2 authors, N D Hall.
Immunology, 1993 Oct 01; 80(2). PMID: 7505258    Free PMC article.
Comparative analysis of B7-1 and B7-2 costimulatory ligands: expression and function.
K S Hathcock, G Laszlo, +2 authors, R J Hodes.
J Exp Med, 1994 Aug 01; 180(2). PMID: 7519245    Free PMC article.
Highly Cited.
CD28 costimulation can promote T cell survival by enhancing the expression of Bcl-XL.
L H Boise, A J Minn, +4 authors, C B Thompson.
Immunity, 1995 Jul 01; 3(1). PMID: 7621080
Highly Cited.
CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation.
M F Krummel, J P Allison.
J Exp Med, 1995 Aug 01; 182(2). PMID: 7543139    Free PMC article.
Highly Cited.
Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4.
P Waterhouse, J M Penninger, +6 authors, T W Mak.
Science, 1995 Nov 10; 270(5238). PMID: 7481803
Highly Cited.
Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4.
E A Tivol, F Borriello, +3 authors, A H Sharpe.
Immunity, 1995 Nov 01; 3(5). PMID: 7584144
Highly Cited.
CD4+ CD7- CD28- T cells are expanded in rheumatoid arthritis and are characterized by autoreactivity.
D Schmidt, J J Goronzy, C M Weyand.
J Clin Invest, 1996 May 01; 97(9). PMID: 8621791    Free PMC article.
Highly Cited.
CTLA-4 ligation blocks CD28-dependent T cell activation.
T L Walunas, C Y Bakker, J A Bluestone.
J Exp Med, 1996 Jun 01; 183(6). PMID: 8676075    Free PMC article.
Highly Cited.
CTLA4Ig prevents lymphoproliferation and fatal multiorgan tissue destruction in CTLA-4-deficient mice.
E A Tivol, S D Boyd, +4 authors, A H Sharpe.
J Immunol, 1997 Jun 01; 158(11). PMID: 9164923
Tyrosine phosphorylation controls internalization of CTLA-4 by regulating its interaction with clathrin-associated adaptor complex AP-2.
T Shiratori, S Miyatake, +4 authors, T Saito.
Immunity, 1997 May 01; 6(5). PMID: 9175836
Interaction of CTLA-4 with the clathrin-associated protein AP50 results in ligand-independent endocytosis that limits cell surface expression.
E Chuang, M L Alegre, +3 authors, C B Thompson.
J Immunol, 1997 Jul 01; 159(1). PMID: 9200449
Dendritic cells and the control of immunity.
J Banchereau, R M Steinman.
Nature, 1998 Apr 01; 392(6673). PMID: 9521319
Highly Cited. Review.
B7-1 or B7-2 is required to produce the lymphoproliferative phenotype in mice lacking cytotoxic T lymphocyte-associated antigen 4 (CTLA-4).
D A Mandelbrot, A J McAdam, A H Sharpe.
J Exp Med, 1999 Jan 20; 189(2). PMID: 9892625    Free PMC article.
Cutting edge: lymphoproliferative disease in the absence of CTLA-4 is not T cell autonomous.
M F Bachmann, G Köhler, +2 authors, M Kopf.
J Immunol, 1999 Jul 22; 163(3). PMID: 10415006
The B7 family revisited.
Rebecca J Greenwald, Gordon J Freeman, Arlene H Sharpe.
Annu Rev Immunol, 2005 Mar 18; 23. PMID: 15771580
Highly Cited. Review.
Exocytosis of CTLA-4 is dependent on phospholipase D and ADP ribosylation factor-1 and stimulated during activation of regulatory T cells.
Karen I Mead, Yong Zheng, +6 authors, David M Sansom.
J Immunol, 2005 Apr 09; 174(8). PMID: 15814706
B7-independent inhibition of T cells by CTLA-4.
Shunsuke Chikuma, Abul K Abbas, Jeffrey A Bluestone.
J Immunol, 2005 Jun 24; 175(1). PMID: 15972645
Lack of intrinsic CTLA-4 expression has minimal effect on regulation of antiviral T-cell immunity.
Dirk Homann, Wolfgang Dummer, +4 authors, Matthias G von Herrath.
J Virol, 2005 Dec 15; 80(1). PMID: 16352552    Free PMC article.
CTLA4Ig: bridging the basic immunology with clinical application.
Jeffrey A Bluestone, E William St Clair, Laurence A Turka.
Immunity, 2006 Mar 21; 24(3). PMID: 16546089
CTLA-4 control over Foxp3+ regulatory T cell function.
Kajsa Wing, Yasushi Onishi, +5 authors, Shimon Sakaguchi.
Science, 2008 Oct 11; 322(5899). PMID: 18845758
Highly Cited.
Transduction of the cytoplasmic domain of CTLA-4 inhibits TcR-specific activation signals and prevents collagen-induced arthritis.
Je-Min Choi, Seung-Hyung Kim, +7 authors, Sang-Kyou Lee.
Proc Natl Acad Sci U S A, 2008 Dec 11; 105(50). PMID: 19066215    Free PMC article.
Ctla-4 controls regulatory T cell peripheral homeostasis and is required for suppression of pancreatic islet autoimmunity.
Emily M Schmidt, Chun Jing Wang, +7 authors, Lucy S K Walker.
J Immunol, 2008 Dec 26; 182(1). PMID: 19109158
CD4+ regulatory T cells require CTLA-4 for the maintenance of systemic tolerance.
Randall H Friedline, David S Brown, +7 authors, Cynthia A Chambers.
J Exp Med, 2009 Feb 04; 206(2). PMID: 19188497    Free PMC article.
Highly Cited.
Genetic evidence that the differential expression of the ligand-independent isoform of CTLA-4 is the molecular basis of the Idd5.1 type 1 diabetes region in nonobese diabetic mice.
Manabu Araki, Denise Chung, +11 authors, Linda S Wicker.
J Immunol, 2009 Sep 29; 183(8). PMID: 19783679    Free PMC article.
CTLA-4 suppresses the pathogenicity of self antigen-specific T cells by cell-intrinsic and cell-extrinsic mechanisms.
Wataru Ise, Masako Kohyama, +5 authors, Kenneth M Murphy.
Nat Immunol, 2009 Dec 29; 11(2). PMID: 20037585    Free PMC article.
Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4.
Omar S Qureshi, Yong Zheng, +12 authors, David M Sansom.
Science, 2011 Apr 09; 332(6029). PMID: 21474713    Free PMC article.
Highly Cited.
Cell-autonomous and -non-autonomous roles of CTLA-4 in immune regulation.
Kajsa Wing, Tomoyuki Yamaguchi, Shimon Sakaguchi.
Trends Immunol, 2011 Jul 05; 32(9). PMID: 21723783
Review.
Regulatory T cells selectively control CD8+ T cell effector pool size via IL-2 restriction.
Wolfgang Kastenmuller, Georg Gasteiger, +5 authors, Ronald N Germain.
J Immunol, 2011 Aug 19; 187(6). PMID: 21849683    Free PMC article.
Novel cancer immunotherapy agents with survival benefit: recent successes and next steps.
Padmanee Sharma, Klaus Wagner, Jedd D Wolchok, James P Allison.
Nat Rev Cancer, 2011 Oct 25; 11(11). PMID: 22020206    Free PMC article.
Highly Cited. Review.
The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses.
Lucy S K Walker, David M Sansom.
Nat Rev Immunol, 2011 Nov 26; 11(12). PMID: 22116087
Highly Cited.
Constitutive clathrin-mediated endocytosis of CTLA-4 persists during T cell activation.
Omar S Qureshi, Satdip Kaur, +8 authors, David M Sansom.
J Biol Chem, 2012 Jan 21; 287(12). PMID: 22262842    Free PMC article.
Cutting edge: cell-extrinsic immune regulation by CTLA-4 expressed on conventional T cells.
Chun Jing Wang, Rupert Kenefeck, +6 authors, Lucy S K Walker.
J Immunol, 2012 Jul 04; 189(3). PMID: 22753931    Free PMC article.
Cutting edge: CTLA-4 on effector T cells inhibits in trans.
Emily Corse, James P Allison.
J Immunol, 2012 Jul 04; 189(3). PMID: 22753941
The B7-independent isoform of CTLA-4 functions to regulate autoimmune diabetes.
Melanie Stumpf, Xuyu Zhou, Jeffrey A Bluestone.
J Immunol, 2013 Jan 08; 190(3). PMID: 23293354    Free PMC article.
Construction of self-recognizing regulatory T cells from conventional T cells by controlling CTLA-4 and IL-2 expression.
Tomoyuki Yamaguchi, Ayumi Kishi, +5 authors, Shimon Sakaguchi.
Proc Natl Acad Sci U S A, 2013 May 22; 110(23). PMID: 23690575    Free PMC article.
Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma.
Tyler R Simpson, Fubin Li, +11 authors, Sergio A Quezada.
J Exp Med, 2013 Jul 31; 210(9). PMID: 23897981    Free PMC article.
Highly Cited.
Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations.
Desirée Schubert, Claudia Bode, +37 authors, Bodo Grimbacher.
Nat Med, 2014 Oct 21; 20(12). PMID: 25329329    Free PMC article.
Highly Cited.
Intranasal delivery of the cytoplasmic domain of CTLA-4 using a novel protein transduction domain prevents allergic inflammation.
Je-Min Choi, Mi-Hyun Ahn, +15 authors, Sang-Kyou Lee.
Nat Med, 2006 Apr 11; 12(5). PMID: 16604087
Cytotoxic T lymphocyte antigen-4-dependent down-modulation of costimulatory molecules on dendritic cells in CD4+ CD25+ regulatory T-cell-mediated suppression.
Cecilia Oderup, Lukas Cederbom, +2 authors, Fredrik Ivars.
Immunology, 2006 Jun 15; 118(2). PMID: 16771859    Free PMC article.
Induction of autoimmune disease in CTLA-4-/- mice depends on a specific CD28 motif that is required for in vivo costimulation.
Xuguang Tai, Francois Van Laethem, Arlene H Sharpe, Alfred Singer.
Proc Natl Acad Sci U S A, 2007 Aug 19; 104(34). PMID: 17702861    Free PMC article.
Co-stimulation and selection for T-cell help for germinal centres: the role of CD28 and OX40.
L S Walker, A Gulbranson-Judge, +2 authors, P J Lane.
Immunol Today, 2000 Jun 29; 21(7). PMID: 10871874
Review.
A SNP in the Immunoregulatory Molecule CTLA-4 Controls mRNA Splicing In Vivo but Does Not Alter Diabetes Susceptibility in the NOD Mouse.
Fabian Jakubczik, Ken Jones, +3 authors, Nick Holmes.
Diabetes, 2015 Oct 10; 65(1). PMID: 26450994    Free PMC article.
Cell Type-Specific Regulation of Immunological Synapse Dynamics by B7 Ligand Recognition.
Joanna Brzostek, Nicholas R J Gascoigne, Vasily Rybakin.
Front Immunol, 2016 Feb 13; 7. PMID: 26870040    Free PMC article.
Review.
Autoimmunity in 2015.
Carlo Selmi.
Clin Rev Allergy Immunol, 2016 Jul 17; 51(1). PMID: 27422713
Review.
Regulatory T Cells in the Tumor Microenvironment and Cancer Progression: Role and Therapeutic Targeting.
Belal Chaudhary, Eyad Elkord.
Vaccines (Basel), 2016 Aug 12; 4(3). PMID: 27509527    Free PMC article.
Highly Cited. Review.
Identifying functional defects in patients with immune dysregulation due to LRBA and CTLA-4 mutations.
Tie Zheng Hou, Nisha Verma, +17 authors, David M Sansom.
Blood, 2017 Feb 06; 129(11). PMID: 28159733    Free PMC article.
iPSC-Derived Regulatory Dendritic Cells Inhibit Allograft Rejection by Generating Alloantigen-Specific Regulatory T Cells.
Songjie Cai, Jiangang Hou, +9 authors, Xiao-Kang Li.
Stem Cell Reports, 2017 Apr 25; 8(5). PMID: 28434942    Free PMC article.
Immune deficiency and autoimmunity in patients with CTLA-4 (CD152) mutations.
N Verma, S O Burns, L S K Walker, D M Sansom.
Clin Exp Immunol, 2017 Jun 11; 190(1). PMID: 28600865    Free PMC article.
Review.
DOCK8 enforces immunological tolerance by promoting IL-2 signaling and immune synapse formation in Tregs.
Erin Janssen, Sudha Kumari, +9 authors, Raif S Geha.
JCI Insight, 2017 Oct 06; 2(19). PMID: 28978806    Free PMC article.
Engineered Tolerance: Tailoring Development, Function, and Antigen-Specificity of Regulatory T Cells.
Nicholas A J Dawson, Jens Vent-Schmidt, Megan K Levings.
Front Immunol, 2017 Nov 23; 8. PMID: 29163527    Free PMC article.
Review.
Requirement of Treg-intrinsic CTLA4/PKCη signaling pathway for suppressing tumor immunity.
Christophe Pedros, Ann J Canonigo-Balancio, Kok-Fai Kong, Amnon Altman.
JCI Insight, 2017 Dec 08; 2(23). PMID: 29212947    Free PMC article.
Lymphocytes in Placental Tissues: Immune Regulation and Translational Possibilities for Immunotherapy.
Tom Erkers, Arwen Stikvoort, Michael Uhlin.
Stem Cells Int, 2018 Jan 20; 2017. PMID: 29348758    Free PMC article.
Review.
A reappraisal of CTLA-4 checkpoint blockade in cancer immunotherapy.
Xuexiang Du, Fei Tang, +14 authors, Yang Liu.
Cell Res, 2018 Feb 24; 28(4). PMID: 29472691    Free PMC article.
Highly Cited.
Description of CD8+ Regulatory T Lymphocytes and Their Specific Intervention in Graft-versus-Host and Infectious Diseases, Autoimmunity, and Cancer.
Martha R Vieyra-Lobato, Jorge Vela-Ojeda, +2 authors, Martha C Moreno-Lafont.
J Immunol Res, 2018 Aug 30; 2018. PMID: 30155493    Free PMC article.
Review.
Characterization of CTLA4 Trafficking and Implications for Its Function.
Sahamoddin Khailaie, Behzad Rowshanravan, +6 authors, Michael Meyer-Hermann.
Biophys J, 2018 Sep 17; 115(7). PMID: 30219287    Free PMC article.
Regulatory T Cells Suppress Effector T Cell Proliferation by Limiting Division Destiny.
Mark R Dowling, Andrey Kan, +3 authors, Edwin D Hawkins.
Front Immunol, 2018 Nov 15; 9. PMID: 30425712    Free PMC article.
Translational Approaches Targeting Ceramide Generation From Sphingomyelin in T Cells to Modulate Immunity in Humans.
Claudia Hollmann, Teresa Wiese, +3 authors, Niklas Beyersdorf.
Front Immunol, 2019 Nov 05; 10. PMID: 31681273    Free PMC article.
Review.
PD-L1:CD80 Cis-Heterodimer Triggers the Co-stimulatory Receptor CD28 While Repressing the Inhibitory PD-1 and CTLA-4 Pathways.
Yunlong Zhao, Calvin K Lee, +8 authors, Enfu Hui.
Immunity, 2019 Nov 24; 51(6). PMID: 31757674    Free PMC article.
Treg-mediated prolonged survival of skin allografts without immunosuppression.
Nina Pilat, Mario Wiletel, +7 authors, Jonathan Sprent.
Proc Natl Acad Sci U S A, 2019 Jun 15; 116(27). PMID: 31196957    Free PMC article.
Versatile and High-throughput Force Measurement Platform for Dorsal Cell Mechanics.
Seungman Park, Yoon Ki Joo, Yun Chen.
Sci Rep, 2019 Sep 19; 9(1). PMID: 31527594    Free PMC article.
CTLA-4: a moving target in immunotherapy.
Behzad Rowshanravan, Neil Halliday, David M Sansom.
Blood, 2017 Nov 10; 131(1). PMID: 29118008    Free PMC article.
Highly Cited. Review.
Immune checkpoint inhibitors.
Enfu Hui.
J Cell Biol, 2019 Feb 15; 218(3). PMID: 30760493    Free PMC article.
Review.
Negative Co-stimulation Constrains T Cell Differentiation by Imposing Boundaries on Possible Cell States.
Spencer C Wei, Roshan Sharma, +8 authors, James P Allison.
Immunity, 2019 Mar 31; 50(4). PMID: 30926234    Free PMC article.
CTLA-4-mediated transendocytosis of costimulatory molecules primarily targets migratory dendritic cells.
Vitalijs Ovcinnikovs, Ellen M Ross, +9 authors, Lucy S K Walker.
Sci Immunol, 2019 Jun 04; 4(35). PMID: 31152091    Free PMC article.
Development of immune checkpoint therapy for cancer.
Jill M Fritz, Michael J Lenardo.
J Exp Med, 2019 May 10; 216(6). PMID: 31068379    Free PMC article.
Highly Cited. Review.
The Pivotal Role of Regulatory T Cells in the Regulation of Innate Immune Cells.
Emeka B Okeke, Jude E Uzonna.
Front Immunol, 2019 Apr 27; 10. PMID: 31024539    Free PMC article.
Review.
MALT1 Proteolytic Activity Suppresses Autoimmunity in a T Cell Intrinsic Manner.
Annelies Demeyer, Ioannis Skordos, +5 authors, Rudi Beyaert.
Front Immunol, 2019 Sep 03; 10. PMID: 31474984    Free PMC article.
A guide to cancer immunotherapy: from T cell basic science to clinical practice.
Alex D Waldman, Jill M Fritz, Michael J Lenardo.
Nat Rev Immunol, 2020 May 21; 20(11). PMID: 32433532    Free PMC article.
Review.
Revisiting the PD-1 pathway.
Nikolaos Patsoukis, Qi Wang, Laura Strauss, Vassiliki A Boussiotis.
Sci Adv, 2020 Sep 20; 6(38). PMID: 32948597    Free PMC article.
Review.
Non-conventional Inhibitory CD4+Foxp3-PD-1hi T Cells as a Biomarker of Immune Checkpoint Blockade Activity.
Roberta Zappasodi, Sadna Budhu, +13 authors, Jedd D Wolchok.
Cancer Cell, 2018 Jun 13; 33(6). PMID: 29894689    Free PMC article.
Highly Cited.
How to evaluate for immunodeficiency in patients with autoimmune cytopenias: laboratory evaluation for the diagnosis of inborn errors of immunity associated with immune dysregulation.
Roshini S Abraham.
Hematology Am Soc Hematol Educ Program, 2020 Dec 05; 2020(1). PMID: 33275711    Free PMC article.
Review.
CD86 Is a Selective CD28 Ligand Supporting FoxP3+ Regulatory T Cell Homeostasis in the Presence of High Levels of CTLA-4.
Neil Halliday, Cayman Williams, +9 authors, David M Sansom.
Front Immunol, 2020 Dec 29; 11. PMID: 33363541    Free PMC article.
Beyond T-Cells: Functional Characterization of CTLA-4 Expression in Immune and Non-Immune Cell Types.
Damilola Oyewole-Said, Vanaja Konduri, +3 authors, William K Decker.
Front Immunol, 2021 Jan 02; 11. PMID: 33384695    Free PMC article.
Review.
CD80 on Human T Cells Is Associated With FoxP3 Expression and Supports Treg Homeostasis.
Blagoje Soskic, Louisa E Jeffery, +8 authors, David M Sansom.
Front Immunol, 2021 Jan 26; 11. PMID: 33488578    Free PMC article.
Modulation of regulatory T cell function and stability by co-inhibitory receptors.
Liliana E Lucca, Margarita Dominguez-Villar.
Nat Rev Immunol, 2020 Apr 10; 20(11). PMID: 32269380
Review.
Ex vivo modelling of PD-1/PD-L1 immune checkpoint blockade under acute, chronic, and exhaustion-like conditions of T-cell stimulation.
Alexander Roberts, Lindsay Bentley, +24 authors, Nicholas M Barnes.
Sci Rep, 2021 Feb 19; 11(1). PMID: 33597595    Free PMC article.
Force-dependent trans-endocytosis by breast cancer cells depletes costimulatory receptor CD80 and attenuates T cell activation.
Seungman Park, Yu Shi, +7 authors, Yun Chen.
Biosens Bioelectron, 2020 Jul 31; 165. PMID: 32729511    Free PMC article.
Inhibition of acid sphingomyelinase increases regulatory T cells in humans.
Teresa Wiese, Fabio Dennstädt, +16 authors, Niklas Beyersdorf.
Brain Commun, 2021 Apr 27; 3(2). PMID: 33898989    Free PMC article.
CD80 Expression on Tumor Cells Alters Tumor Microenvironment and Efficacy of Cancer Immunotherapy by CTLA-4 Blockade.
Julie Vackova, Ingrid Polakova, Shweta Dilip Johari, Michal Smahel.
Cancers (Basel), 2021 May 01; 13(8). PMID: 33923750    Free PMC article.
Construction of an immune-related LncRNA signature with prognostic significance for bladder cancer.
Wen-Jie Luo, Xi Tian, +7 authors, Yi-Ping Zhu.
J Cell Mol Med, 2021 Apr 03; 25(9). PMID: 33797188    Free PMC article.
PD-L1 signaling on human memory CD4+ T cells induces a regulatory phenotype.
Giorgia Fanelli, Marco Romano, +11 authors, Pablo D Becker.
PLoS Biol, 2021 Apr 27; 19(4). PMID: 33901179    Free PMC article.
Immune checkpoint deficiencies and autoimmune lymphoproliferative syndromes.
Laura Gámez-Díaz, Bodo Grimbacher.
Biomed J, 2021 Aug 14; 44(4). PMID: 34384744    Free PMC article.
Review.
Our current understanding of checkpoint inhibitor therapy in cancer immunotherapy.
Elena Goleva, Taras Lyubchenko, +3 authors, Jeffrey A Kern.
Ann Allergy Asthma Immunol, 2021 Mar 16; 126(6). PMID: 33716146    Free PMC article.
Review.
Rap1 prevents colitogenic Th17 cell expansion and facilitates Treg cell differentiation and distal TCR signaling.
Sayaka Ishihara, Tsuyoshi Sato, +5 authors, Koko Katagiri.
Commun Biol, 2022 Mar 06; 5(1). PMID: 35246619    Free PMC article.
T-cell trans-synaptic vesicles are distinct and carry greater effector content than constitutive extracellular vesicles.
Pablo F Céspedes, Ashwin Jainarayanan, +23 authors, Michael L Dustin.
Nat Commun, 2022 Jun 18; 13(1). PMID: 35710644