The role of CD28 and cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) in regulatory T‐cell biology

Innate Immune Recognition

2002 • 8,157 citations

Control of Regulatory T Cell Development by the Transcription Factor Foxp3

2003 • 7,902 citations

Foxp3 programs the development and function of CD4+CD25+ regulatory T cells

2003 • 7,470 citations

Conversion of Peripheral CD4+CD25− Naive T Cells to CD4+CD25+ Regulatory T Cells by TGF-β Induction of Transcription Factor Foxp3

2003 • 4,529 citations

Toll-like receptor control of the adaptive immune responses

2004 • 4,092 citations

bcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death

1993 • 3,111 citations

Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4

1995 • 2,842 citations

An essential role for Scurfin in CD4+CD25+ T regulatory cells

2003 • 2,825 citations

Regulatory T Cell Lineage Specification by the Forkhead Transcription Factor Foxp3

2005 • 2,256 citations

Cytotoxic T Lymphocyte–Associated Antigen 4 Plays an Essential Role in the Function of Cd25+Cd4+ Regulatory Cells That Control Intestinal Inflammation

2000 • 2,211 citations

Immunologic Self-Tolerance Maintained by Cd25+Cd4+Regulatory T Cells Constitutively Expressing Cytotoxic T Lymphocyte–Associated Antigen 4

2000 • 2,207 citations

CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation.

1995 • 2,090 citations

B7/CD28 Costimulation Is Essential for the Homeostasis of the CD4+CD25+ Immunoregulatory T Cells that Control Autoimmune Diabetes

2000 • 2,090 citations

A function for interleukin 2 in Foxp3-expressing regulatory T cells

2005 • 1,744 citations

Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide

2001 • 1,659 citations

The B7–CD28 superfamily

2002 • 1,646 citations

Cell Contact–Dependent Immunosuppression by Cd4+Cd25+Regulatory T Cells Is Mediated by Cell Surface–Bound Transforming Growth Factor β

2001 • 1,609 citations

Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state.

1998 • 1,579 citations

Regulatory T cells mediate maternal tolerance to the fetus

2004 • 1,568 citations

Modulation of tryptophan catabolism by regulatory T cells

2003 • 1,323 citations

Differential T Cell Costimulatory Requirements in CD28-Deficient Mice

1993 • 1,271 citations

Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25– T cells

2003 • 1,252 citations

Inducing and expanding regulatory T cell populations by foreign antigen

2005 • 1,245 citations

Thymus and Autoimmunity: Production of CD25+CD4+ Naturally Anergic and Suppressive T Cells as a Key Function of the Thymus in Maintaining Immunologic Self-Tolerance

1999 • 1,223 citations

In Vitro–expanded Antigen-specific Regulatory T Cells Suppress Autoimmune Diabetes

2004 • 1,192 citations

Homeostatic maintenance of natural Foxp3+ CD25+ CD4+ regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization

2005 • 1,189 citations

Regulated transport of the glucose transporter GLUT4

2002 • 1,154 citations

CTLA-4–Ig regulates tryptophan catabolism in vivo

2002 • 1,150 citations

Cutting Edge: TGF-β Induces a Regulatory Phenotype in CD4+CD25− T Cells through Foxp3 Induction and Down-Regulation of Smad7

2004 • 1,123 citations

Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self

2001 • 1,043 citations

Potential Regulatory Function of Human Dendritic Cells Expressing Indoleamine 2,3-Dioxygenase

2002 • 1,035 citations

Complexities of CD28/B7: CTLA-4 Costimulatory Pathways in Autoimmunity and Transplantation

2001 • 1,032 citations

Human Cd25+Cd4+ T Regulatory Cells Suppress Naive and Memory T Cell Proliferation and Can Be Expanded in Vitro without Loss of Function

2001 • 1,008 citations

TGF-β1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells

2005 • 955 citations

Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors

1994 • 950 citations

B70 antigen is a second ligand for CTLA-4 and CD28

1993 • 907 citations

Direct Expansion of Functional CD25+ CD4+ Regulatory T Cells by Antigen-processing Dendritic Cells

2003 • 893 citations

T-cell regulation by CD28 and CTLA-4

2001 • 857 citations

Clathrin- and non-clathrin-mediated endocytic regulation of cell signalling

2005 • 852 citations

Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells

2004 • 805 citations

CTLA-4 ligation blocks CD28-dependent T cell activation.

1996 • 787 citations

Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice

2005 • 783 citations

CD25+CD4+ Regulatory T Cells Prevent Graft Rejection: CTLA-4- and IL-10-Dependent Immunoregulation of Alloresponses

2002 • 766 citations

Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus

2005 • 743 citations

Normal human pregnancy is associated with an elevation in the immune suppressive CD25⁺ CD4⁺ regulatory T‐cell subset

2004 • 727 citations

In Vivo Instruction of Suppressor Commitment in Naive T Cells

2004 • 726 citations

Recognition of the Peripheral Self by Naturally Arising CD25+ CD4+ T Cell Receptors

2004 • 690 citations

Molecular Basis of T Cell Inactivation by CTLA-4

1998 • 678 citations

Cutting Edge: CD28 Controls Peripheral Homeostasis of CD4+CD25+ Regulatory T Cells

2003 • 674 citations

CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines.

1989 • 662 citations

Natural and Induced CD4+CD25+ Cells Educate CD4+CD25− Cells to Develop Suppressive Activity: The Role of IL-2, TGF-β, and IL-10

2004 • 657 citations

IL-10-Secreting Regulatory T Cells Do Not Express Foxp3 but Have Comparable Regulatory Function to Naturally Occurring CD4+CD25+ Regulatory T Cells

2004 • 654 citations

TGF-β1 Plays an Important Role in the Mechanism of CD4+CD25+ Regulatory T Cell Activity in Both Humans and Mice

2004 • 643 citations

The Interaction Properties of Costimulatory Molecules Revisited

2002 • 640 citations

The tissue distribution of the B7-2 costimulator in mice: abundant expression on dendritic cells in situ and during maturation in vitro.

1994 • 607 citations

Antigen-dependent Proliferation of CD4+ CD25+ Regulatory T Cells In Vivo

2003 • 600 citations

CD28 costimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2

2005 • 591 citations

Identifying Foxp3-expressing suppressor T cells with a bicistronic reporter

2005 • 583 citations

Intracellular Trafficking of CTLA-4 and Focal Localization Towards Sites of TCR Engagement

1996 • 583 citations

Promiscuous gene expression in thymic epithelial cells is regulated at multiple levels

2005 • 540 citations

TGF-β Induces Foxp3 + T-Regulatory Cells from CD4 + CD25 − Precursors

2004 • 527 citations

Continuous Activation of Autoreactive CD4+ CD25+ Regulatory T Cells in the Steady State

2003 • 523 citations

B7-1 and B7-2 Have Overlapping, Critical Roles in Immunoglobulin Class Switching and Germinal Center Formation

1997 • 499 citations

Cytotoxic T Lymphocyte Antigen-4 Accumulation in the Immunological Synapse Is Regulated by TCR Signal Strength

2002 • 497 citations

Development and function of agonist-induced CD25+Foxp3+ regulatory T cells in the absence of interleukin 2 signaling

2005 • 473 citations

Generation Ex Vivo of TGF-β-Producing Regulatory T Cells from CD4+CD25− Precursors

2002 • 461 citations

Ligation of B7-1/B7-2 by Human CD4+ T Cells Triggers Indoleamine 2,3-Dioxygenase Activity in Dendritic Cells

2004 • 459 citations

Prevention of T cell–driven complement activation and inflammation by tryptophan catabolism during pregnancy

2001 • 425 citations

Developmental regulation of Foxp3 expression during ontogeny

2005 • 418 citations

B7-1 and B7-2 Selectively Recruit CTLA-4 and CD28 to the Immunological Synapse

2004 • 415 citations

CTLA-4 Regulates Induction of Anergy In Vivo

2001 • 409 citations

The Role of IL-10 and TGF-β in the Differentiation and Effector Function of T Regulatory Cells

2002 • 408 citations

Cutting Edge: TGF-β Signaling Is Required for the In Vivo Expansion and Immunosuppressive Capacity of Regulatory CD4+CD25+ T Cells

2004 • 395 citations

Anergic T Cells as Suppressor Cells in Vitro

1994 • 389 citations

In vivodynamics of antigen-specific regulatory T cells not predicted from behaviorin vitro

2003 • 384 citations

TGF-beta 1 prevents the noncognate maturation of human dendritic Langerhans cells.

1999 • 379 citations

Distinct roles of CTLA‐4 and TGF‐β in CD4⁺CD25⁺ regulatory T cell function

2004 • 377 citations

CD25− T Cells Generate CD25+Foxp3+ Regulatory T Cells by Peripheral Expansion

2004 • 373 citations

Engagement of Cytotoxic T Lymphocyte–associated Antigen 4 (CTLA-4) Induces Transforming Growth Factor β (TGF-β) Production by Murine CD4+ T Cells

1998 • 359 citations

Regulation of surface and intracellular expression of CTLA4 on mouse T cells.

1996 • 340 citations

Self-representation in the thymus: an extended view

2004 • 339 citations

Tyrosine Phosphorylation Controls Internalization of CTLA-4 by Regulating Its Interaction with Clathrin-Associated Adaptor Complex AP-2

1997 • 334 citations

Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease

2004 • 322 citations

CD28, CTLA‐4 and their ligands: who does what and to whom?

2000 • 317 citations

Activation requirements for the induction of CD4⁺CD25⁺ T cell suppressor function

2004 • 307 citations

TGF-β1 Prevents the Noncognate Maturation of Human Dendritic Langerhans Cells

1999 • 303 citations

T cell anergy and costimulation

2003 • 299 citations

Specific subsets of murine dendritic cells acquire potent T cell regulatory functions following CTLA4-mediated induction of indoleamine 2,3 dioxygenase

2004 • 290 citations

De novogeneration of antigen-specific CD4⁺CD25⁺regulatory T cells from human CD4⁺CD25^–cells

2005 • 284 citations

Interleukin‐10 differentially regulates B7‐1 (CD80) and B7‐2 (CD86) expression on human peripheral blood dendritic cells

1995 • 282 citations

Compromised Ox40 Function in Cd28-Deficient Mice Is Linked with Failure to Develop Cxc Chemokine Receptor 5–Positive Cd4 Cells and Germinal Centers

1999 • 275 citations

CD86 and CD80 Differentially Modulate the Suppressive Function of Human Regulatory T Cells

2004 • 275 citations

The B7/BB1 antigen provides one of several costimulatory signals for the activation of CD4+ T lymphocytes by human blood dendritic cells in vitro.

1992 • 273 citations

Functional expression of B7/BB1 on activated T lymphocytes.

1993 • 271 citations

Conversion of CD4+ CD25− cells into CD4+ CD25+ regulatory T cells in vivo requires B7 costimulation, but not the thymus

2005 • 271 citations

Functional expression of indoleamine 2,3-dioxygenase by murine CD8α+ dendritic cells

2002 • 251 citations

A cellular calculus for signal integration by T cells

2000 • 243 citations

Structure and Dimerization of a Soluble Form of B7-1

2000 • 240 citations

B7/CD28-Dependent CD4+CD25+ Regulatory T Cells Are Essential Components of the Memory-Protective Immunity to Candida albicans

2002 • 236 citations

Structural Analysis of CTLA-4 Function In Vivo

2000 • 236 citations

Cutting Edge: Lymphoproliferative Disease in the Absence of CTLA-4 Is Not T Cell Autonomous

1999 • 236 citations

Foxp3⁺CD25^–CD4 T cells constitute a reservoir of committed regulatory cells that regain CD25 expression upon homeostatic expansion

2005 • 228 citations

Control of Foxp3+ CD25+CD4+ regulatory cell activation and function by dendritic cells

2004 • 226 citations

An Autoimmune Disease-Associated CTLA-4 Splice Variant Lacking the B7 Binding Domain Signals Negatively in T Cells

2004 • 212 citations

A point mutation in CD28 distinguishes proliferative signals from survival signals

2001 • 210 citations

Selective targeting of regulatory T cells with CD28 superagonists allows effective therapy of experimental autoimmune encephalomyelitis

2005 • 202 citations

Efficient expansion of regulatory T cells in vitro and in vivo with a CD28 superagonist

2003 • 186 citations

Toward the identification of a tolerogenic signature in IDO-competent dendritic cells

2005 • 184 citations

In vitro expanded human CD4+CD25+ regulatory T cells suppress effector T cell proliferation

2005 • 182 citations

The inhibitory function of B7 costimulators in T cell responses to foreign and self-antigens

2003 • 177 citations

Anergic T Cells Inhibit the Antigen-Presenting Function of Dendritic Cells

2000 • 173 citations

Costimulation controls diabetes by altering the balance of pathogenic and regulatory T cells

2004 • 150 citations

Thymocyte development is normal in CTLA-4-deficient mice

1997 • 147 citations

Regulation of Cell Surface Expression of CTLA-4 by Secretion of CTLA-4-Containing Lysosomes Upon Activation of CD4+ T Cells

2000 • 146 citations

Regulatory T Cells, Derived from Naïve CD4+CD25− T Cells by In Vitro Foxp3 Gene Transfer, Can Induce Transplantation Tolerance

2005 • 143 citations

Costimulation controls diabetes by altering the balance of pathogenic and regulatory T cells

2004 • 141 citations

Cytolytic T lymphocyte-associated antigen-4 and the TCR zeta/CD3 complex, but not CD28, interact with clathrin adaptor complexes AP-1 and AP-2.

1999 • 138 citations

Inhibition of human T cell proliferation by CTLA-4 utilizes CD80 and requires CD25+ regulatory T cells

2002 • 137 citations

Cytotoxic T Lymphocyte Antigen 4 and CD28 Modulate Cell Surface Raft Expression in Their Regulation of T Cell Function

2001 • 136 citations

B7 Expression on T Cells Down-Regulates Immune Responses through CTLA-4 Ligation via R-T Interactions

2004 • 129 citations

Suppressive properties of human CD4⁺CD25⁺ regulatory T cells are dependent on CTLA‐4 expression

2004 • 126 citations

Negative Regulation of T Cell Receptor–Lipid Raft Interaction by Cytotoxic T Lymphocyte–associated Antigen 4

2003 • 122 citations

Ligation of CD28 receptor by B7 induces formation of D‐3 phosphoinositides in T lymphocytes independently of T cell receptor/CD3 activation

1993 • 121 citations

CTLA-4 up-regulation of lymphocyte function-associated antigen 1 adhesion and clustering as an alternate basis for coreceptor function

2005 • 120 citations

B7/BB1, the ligand for CD28, is expressed on repeatedly activated human T cells in vitro

1993 • 117 citations

Acquisition of anergic and suppressive activities in transforming growth factor- -costimulated CD4+CD25- T cells

2004 • 116 citations

Regulation of Cytotoxic T Lymphocyte-Associated Molecule-4 by Src Kinases

1999 • 115 citations

Secondary but not primary T cell responses are enhanced in CTLA-4-deficient CD8+ T cells

1998 • 115 citations

Cytolytic T Lymphocyte-Associated Antigen-4 and the TCRζ/CD3 Complex, But Not CD28, Interact with Clathrin Adaptor Complexes AP-1 and AP-2

1999 • 113 citations

TGF regulates the CD4+CD25+ T-cell pool and the expression of Foxp3 in vivo

2004 • 106 citations

Surface Cytotoxic T Lymphocyte–associated Antigen 4 Partitions Within Lipid Rafts and Relocates to the Immunological Synapse under Conditions of Inhibition of T Cell Activation

2002 • 106 citations

Induction of Cytotoxic T Lymphocyte Antigen 4 (Ctla-4) <u>Restricts</u> Clonal Expansion of Helper T Cells

2001 • 105 citations

Regulation of human auto- and alloreactive T cells by indoleamine 2,3-dioxygenase (IDO)–producing dendritic cells: too much ado about IDO?

2004 • 99 citations

Cytotoxic T Lymphocyte Antigen 4 (Ctla-4) Engagement Delivers an Inhibitory Signal through the Membrane-Proximal Region in the Absence of the Tyrosine Motif in the Cytoplasmic Tail

1999 • 96 citations

SKIN ALLOGRAFT REJECTION IN CD28-DEFICIENT MICE1

1996 • 93 citations

Co-stimulation and selection for T-cell help for germinal centres: the role of CD28 and OX40

2000 • 93 citations

Cutting Edge: Silencing Suppressor of Cytokine Signaling 3 Expression in Dendritic Cells Turns CD28-Ig from Immune Adjuvant to Suppressant

2005 • 91 citations

Anergic T cells effect linked suppression

1997 • 87 citations

A Role for the B7-1/B7-2:CD28/CTLA-4 Pathway During Negative Selection

2003 • 83 citations

The Inhibitory Function of CTLA-4 Does Not Require Its Tyrosine Phosphorylation

2000 • 81 citations

Exocytosis of CTLA-4 Is Dependent on Phospholipase D and ADP Ribosylation Factor-1 and Stimulated during Activation of Regulatory T Cells

2005 • 81 citations

B7.2 expressed by T cells does not induce CD28-mediated costimulatory activity but retains CTLA4 binding: implications for induction of antitumor immunity to T cell tumors.

1997 • 78 citations

CD28 disruption exacerbates inflammation in Tgf-β1-/- mice: in vivo suppression by CD4+CD25+ regulatory T cells independent of autocrine TGF-β1

2004 • 78 citations

B7-Independent Inhibition of T Cells by CTLA-4

2005 • 74 citations

Normal thymic selection, normal viability and decreased lymphoproliferation in T cell receptor‐transgenic CTLA‐4‐deficient mice

1997 • 74 citations

CD25+CD4+ regulatory T cells exert in vitro suppressive activity independent of CTLA-4

2005 • 71 citations

Human Effector Memory T Cells Express CD86: A Functional Role in Naive T Cell Priming

1999 • 67 citations

CD28 Regulates the Translation of Bcl-xL via the Phosphatidylinositol 3-Kinase/Mammalian Target of Rapamycin Pathway

2005 • 66 citations

Expression of a hypoglycosylated form of CD86 (B7-2) on human T cells with altered binding properties to CD28 and CTLA-4.

1997 • 64 citations

Activation of Human T Cells with Superantigen (Staphylococcal Enterotoxin B) and CD28 Confers Resistance to Apoptosis via CD95

1998 • 64 citations

Integration of CD28 and CTLA‐4 function results in differential responses of T cells to CD80 and CD86

2006 • 64 citations

Regulated Costimulation in the Thymus Is Critical for T Cell Development: Dysregulated CD28 Costimulation Can Bypass the Pre-TCR Checkpoint

2005 • 59 citations

Lack of a role for transforming growth factor-β in cytotoxic T lymphocyte antigen-4-mediated inhibition of T cell activation

2001 • 57 citations

An Important Role of CD80/CD86-CTLA-4 Signaling during Photocarcinogenesis in Mice

2005 • 53 citations

Re-establishing Peripheral Tolerance in the Absence of CTLA-4: Complementation by Wild-Type T Cells Points to an Indirect Role for CTLA-4

2002 • 51 citations

Opening a Window on Thymic Positive Selection: Developmental Changes in the Influence of Cosignaling by Integrins and CD28 on Selection Events Induced by TCR Engagement

2000 • 43 citations

Role of CD28 co-stimulation in generation and maintenance of virus-specific T cells

2002 • 41 citations

Expression of B7 Costimulator Molecules on Mouse Dendritic Cells

1995 • 40 citations

In vivo overexpression of CTLA‐4 suppresses lymphoproliferative diseases and thymic negative selection

2005 • 39 citations

Policing pregnancy: Tregs help keep the peace

2004 • 32 citations

CTLA-4 Is Important in Maintaining Long-Term Survival of Cardiac Allografts

2005 • 21 citations

B7-CD28 Interaction Promotes Proliferation and Survival but Suppresses Differentiation of CD4−CD8− T Cells in the Thymus

2004 • 20 citations

Thymic selection can compensate for mutations affecting T cell activation and generate a normal T cell repertoire in mutant mice

2003 • 4 citations