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CD28 Costimulation Of Developing Thymocytes Induces Foxp3 Expression And Regulatory T Cell Differentiation Independently Of Interleukin 2

X. Tai, M. Cowan, L. Feigenbaum, A. Singer
Published 2005 · Biology, Medicine

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Efficient generation of regulatory T cells (Treg cells) in the thymus requires CD28 costimulation, but it is not known why. Here, molecular mapping of CD28 costimulation showed that Treg cell generation requires a motif that binds the tyrosine kinase Lck, precisely the same motif that is required for CD28 costimulation of interleukin 2 production. Nevertheless, CD28 costimulation provides more than interleukin 2 to developing Treg cells, as CD28 costimulation of T cell receptor–signaled double-positive thymocytes induced expression of Foxp3, considered to be the Treg 'master gene', as well as GITR and CTLA-4, two proteins expressed on Treg cells. Thus, CD28 costimulation directly signals developing thymocytes to express Foxp3 and to initiate the Treg cell differentiation program.
This paper references
10.1016/0092-8674(88)90578-8
The effect of thymus environment on T cell development and tolerance
P. Marrack (1988)
10.1126/SCIENCE.2511629
A nondeletional mechanism of thymic self tolerance.
F. Ramsdell (1989)
10.1038/341746A0
Selective development of CD4+ T cells in transgenic mice expressing a class II MHC-restricted antigen receptor
J. Kaye (1989)
10.1084/JEM.171.3.935
Clonal deletion and clonal anergy in the thymus induced by cellular elements with different radiation sensitivities
J. Roberts (1990)
CD28 delivers a costimulatory signal involved in antigen-specific IL-2 production by human T cells.
M. Jenkins (1991)
10.1016/0092-8674(91)90361-2
bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes
C. Sentman (1991)
10.1126/SCIENCE.7688139
Differential T cell costimulatory requirements in CD28-deficient mice.
A. Shahinian (1993)
10.1038/370157a0
Binding of phosphatidylinositol-3-OH kinase to CD28 is required for T-cell signalling
F. Pagès (1994)
10.1038/369327A0
Binding of phosphatidyl-inositol-3-OH kinase to CD28 is required for T-cell signalling
F. Pagès (1994)
10.1073/PNAS.91.7.2834
T-cell antigen CD28 interacts with the lipid kinase phosphatidylinositol 3-kinase by a cytoplasmic Tyr(P)-Met-Xaa-Met motif.
K. S. Prasad (1994)
10.1084/JEM.179.2.709
Negative selection of CD4+CD8+ thymocytes by T cell receptor-induced apoptosis requires a costimulatory signal that can be provided by CD28
J. Punt (1994)
10.1016/1074-7613(95)90149-3
Asymmetric signaling requirements for thymocyte commitment to the CD4+ versus CD8+ T cell lineages: a new perspective on thymic commitment and selection.
H. Suzuki (1995)
10.1016/1074-7613(95)90161-2
CD28 costimulation can promote T cell survival by enhancing the expression of Bcl-XL.
L. Boise (1995)
10.1084/JEM.183.6.2617
Antigen compartmentation and T helper cell tolerance induction
S. Oehen (1996)
10.1016/S1074-7613(00)80327-1
Surface molecules that drive T cell development in vitro in the absence of thymic epithelium and in the absence of lineage-specific signals.
R. Cibotti (1997)
10.1084/JEM.186.11.1911
T Cell Receptor (TCR)-induced Death of Immature CD4+CD8+ Thymocytes by Two Distinct Mechanisms Differing in Their Requirement for CD28 Costimulation: Implications for Negative Selection in the Thymus
J. Punt (1997)
The SH3 domain of Itk/Emt binds to proline-rich sequences in the cytoplasmic domain of the T cell costimulatory receptor CD28.
L. Marengere (1997)
10.1093/INTIMM/10.4.371
Regulatory CD4 T cells: expression of IL-2R alpha chain, resistance to clonal deletion and IL-2 dependency.
M. Papiernik (1998)
Regulatory CD4 T cells: expression of IL-2Ra chain, resistance to clonal deletion and IL-2
M. Papiernik (1998)
10.1084/JEM.190.1.65
Several Different Cell Surface Molecules Control Negative Selection of Medullary Thymocytes
H. Kishimoto (1999)
10.1084/JEM.190.3.375
Proline Residues in Cd28 and the Src Homology (Sh)3 Domain of Lck Are Required for T Cell Costimulation
A. Holdorf (1999)
10.1126/SCIENCE.283.5402.680
T lymphocyte costimulation mediated by reorganization of membrane microdomains.
A. Viola (1999)
10.1016/S1074-7613(00)00008-X
Coreceptor reversal in the thymus: signaled CD4+8+ thymocytes initially terminate CD8 transcription even when differentiating into CD8+ T cells.
E. Brugnera (2000)
10.1016/S1074-7613(00)80195-8
B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes.
B. Salomon (2000)
10.1084/JEM.192.2.303
Immunologic Self-Tolerance Maintained by Cd25+Cd4+Regulatory T Cells Constitutively Expressing Cytotoxic T Lymphocyte–Associated Antigen 4
Takeshi Takahashi (2000)
10.1084/JEM.192.2.295
Cytotoxic T Lymphocyte–Associated Antigen 4 Plays an Essential Role in the Function of Cd25+Cd4+ Regulatory Cells That Control Intestinal Inflammation
S. Read (2000)
Immunologic selftolerance maintained by CD 25 + CD 4 + regulatory T cells constitutively expressing cytotoxic T lymphocyteassociated antigen 4
T. Takahashi (2000)
10.1038/35105024
T-cell regulation by CD28 and CTLA-4
M. Alegre (2001)
10.1038/87789
Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide
M. Jordan (2001)
10.1038/86327
A point mutation in CD28 distinguishes proliferative signals from survival signals
K. Okkenhaug (2001)
10.4049/jimmunol.166.5.3468
Maturation Versus Death of Developing Double-Positive Thymocytes Reflects Competing Effects on Bcl-2 Expression and Can Be Regulated by the Intensity of CD28 Costimulation1
D. Mckean (2001)
10.1084/JEM.194.4.427
Major Histocompatibility Complex Class II–Positive Cortical Epithelium Mediates the Selection of Cd4+25+ Immunoregulatory T Cells
S. Bensinger (2001)
10.1034/j.1600-065X.2001.1820102.x
Immunologic tolerance maintained by CD25+ CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance
S. Sakaguchi (2001)
10.4049/jimmunol.166.9.5331
Cutting Edge: Distinct Motifs Within CD28 Regulate T Cell Proliferation and Induction of Bcl-XL1
J. S. Burr (2001)
10.1034/j.1600-065X.2001.1820104.x
Control of T‐cell activation by CD4+ CD25+ suppressor T cells
E. Shevach (2001)
10.4049/jimmunol.166.6.3797
Critical Requirement for the Membrane-Proximal Cytosolic Tyrosine Residue for CD28-Mediated Costimulation In Vivo1
Y. Harada (2001)
10.1038/ni759
Stimulation of CD25+CD4+ regulatory T cells through GITR breaks immunological self-tolerance
J. Shimizu (2002)
10.1016/S1074-7613(02)00367-9
CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rbeta-deficient mice. Implications for the nonredundant function of IL-2.
T. Malek (2002)
10.1016/S1074-7613(02)00280-7
CD4(+)CD25(+) immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor.
R. McHugh (2002)
10.1038/nri727
The B7–CD28 superfamily
A. Sharpe (2002)
10.1038/ni761
Regulation of Lck activity by CD4 and CD28 in the immunological synapse
A. Holdorf (2002)
10.1038/ni816
Origin of regulatory T cells with known specificity for antigen
I. Apostolou (2002)
10.4049/jimmunol.169.9.4850
Homeostasis of Peripheral CD4+ T Cells: IL-2Rα and IL-2 Shape a Population of Regulatory Cells That Controls CD4+ T Cell Numbers1
A. M. Almeida (2002)
10.1038/nri701
The enemy within: keeping self-reactive T cells at bay in the periphery
L. Walker (2002)
10.1038/nri821
CD4+CD25+ suppressor T cells: more questions than answers
E. Shevach (2002)
10.1016/S1074-7613(02)00417-X
Peripheral expression of self-MHC-II influences the reactivity and self-tolerance of mature CD4(+) T cells: evidence from a lymphopenic T cell model.
A. Bhandoola (2002)
10.4049/jimmunol.171.7.3348
Cutting Edge: CD28 Controls Peripheral Homeostasis of CD4+CD25+ Regulatory T Cells 1
Q. Tang (2003)
10.1038/ni904
Foxp3 programs the development and function of CD4+CD25+ regulatory T cells
J. Fontenot (2003)
10.1038/ni909
An essential role for Scurfin in CD4+CD25+ T regulatory cells
R. Khattri (2003)
10.1126/SCIENCE.1079490
Control of Regulatory T Cell Development by the Transcription Factor Foxp3
S. Hori (2003)
10.1146/ANNUREV.IMMUNOL.21.120601.141122
Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses.
S. Sakaguchi (2004)
10.1038/ni1044
Distinct regions in the CD28 cytoplasmic domain are required for T helper type 2 differentiation
P. Andres (2004)



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J. Srinivasan (2021)
10.3389/fimmu.2021.643153
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Jérémy C. Santamaria (2021)
10.1007/978-981-15-6407-9_2
A Structure-Guided Delineation of FOXP3 Regulation Mechanism in IPEX.
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10.3389/fimmu.2021.688460
Harnessing Mechanisms of Immune Tolerance to Improve Outcomes in Solid Organ Transplantation: A Review
P. F. Slepicka (2021)
10.1111/ajt.16724
In vivo Treg expansion under costimulation blockade targets early rejection and improves long-term outcome.
C. Schwarz (2021)
10.1007/978-981-15-6407-9_3
Regulation of Treg Functions by the Ubiquitin Pathway.
E. Montauti (2021)
10.1084/jem.20192423
miR-155 promotes T reg cell development by safeguarding medullary thymic epithelial cell maturation
Jiayi Dong (2021)
10.1007/978-981-15-6407-9_9
Intestinal Regulatory T Cells.
Vanessa Figliuolo da Paz (2021)
10.1136/jitc-2021-002339
FOXP3-based immune risk model for recurrence prediction in small-cell lung cancer at stages I–III
Minlin Jiang (2021)
10.1155/2021/8816055
Critical Roles of Balanced T Helper 9 Cells and Regulatory T Cells in Allergic Airway Inflammation and Tumor Immunity
Muhua Huang (2021)
10.1007/978-981-15-6407-9_13
TNF-TNFR2 Signal Plays a Decisive Role in the Activation of CD4+Foxp3+ Regulatory T Cells: Implications in the Treatment of Autoimmune Diseases and Cancer.
Md. Sahidul Islam (2021)
10.3389/fonc.2021.621639
Treatment-Related Serious Adverse Events of Immune Checkpoint Inhibitors in Clinical Trials: A Systematic Review
T. Ouyang (2021)
10.3390/cells10081847
Translating Treg Therapy for Inflammatory Bowel Disease in Humanized Mice
S. Negi (2021)
10.1101/2021.08.27.457792
The thymic microenvironment gradually modulates the phenotype of thymus-homing peripheral conventional dendritic cells
Susanne Herppich (2021)
10.1016/j.lfs.2021.119132
The role of regulatory T cells in the pathogenesis and treatment of prostate cancer.
Vahid Karpisheh (2021)
10.1155/2020/1387952
Erythromycin Suppresses the Cigarette Smoke Extract-Exposed Dendritic Cell-Mediated Polarization of CD4+ T Cells into Th17 Cells
Jifeng Liu (2020)
10.1111/ctr.13834
Differential gene expression in non‐adherent heart transplant survivors: Implications for regulatory T‐cell expression
D. Baran (2020)
10.1111/ajt.16218
CTLA4‐Ig prolongs graft survival specifically in young but not old mice
T. Heinbokel (2020)
10.1111/imm.13178
Control of regulatory T‐cell differentiation and function by T‐cell receptor signalling and Foxp3 transcription factor complexes
M. Ono (2020)
10.1186/s13104-020-05427-1
Epigenetic mechanisms shape the underlining expression regulatory mechanisms of the STAT3 in multiple sclerosis disease
A. Hosseini (2020)
10.3389/fimmu.2020.00723
Role of Regulatory T Cells in Disturbed Immune Homeostasis in Patients With Chronic Obstructive Pulmonary Disease
Jia Hou (2020)
10.1002/eji.201948270
Harnessing proteases for T regulatory cell immunotherapy
S. Amarnath (2020)
10.1038/s41467-020-17544-3
Differential expression of tissue-restricted antigens among mTEC is associated with distinct autoreactive T cell fates
Marie-Ève Lebel (2020)
10.1016/j.cellimm.2020.104236
Regulating the regulators: Is introduction of an antigen-specific approach in regulatory T cells the next step to treat autoimmunity?
I. Janssens (2020)
10.1007/978-981-15-3350-1_8
Role of Regulatory T Lymphocytes in Health and Disease
Niti Shokeen (2020)
10.3389/fphar.2020.588436
Intrahepatic TH17/TReg Cells in Homeostasis and Disease—It’s All About the Balance
Hannah K Drescher (2020)
10.3389/fimmu.2020.600000
CD86 Is a Selective CD28 Ligand Supporting FoxP3+ Regulatory T Cell Homeostasis in the Presence of High Levels of CTLA-4
Neil Halliday (2020)
10.1002/eji.202048743
Robust intrathymic development of regulatory T cells in young NOD mice is rapidly restrained by recirculating cells
Julie Darrigues (2020)
10.1073/pnas.1922600117
Epigenetic conversion of conventional T cells into regulatory T cells by CD28 signal deprivation
Norihisa Mikami (2020)
10.1016/j.isci.2020.101421
The Cytokine Receptor IL-7Rα Impairs IL-2 Receptor Signaling and Constrains the In Vitro Differentiation of Foxp3+ Treg Cells
A. Waickman (2020)
10.1186/s12979-020-00202-z
The correlation between the Th17/Treg cell balance and bone health
Lei Zhu (2020)
10.3389/fimmu.2020.01519
The CD28 Transmembrane Domain Contains an Essential Dimerization Motif
S. Leddon (2020)
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