CTLA-4: new insights into its biological function and use in tumor immunotherapy

Enhancement of Antitumor Immunity by CTLA-4 Blockade

1996 • 3,585 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

Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity.

1993 • 2,828 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

CTLA-4 can function as a negative regulator of T cell activation

1994 • 2,107 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

CTLA-4 is a second receptor for the B cell activation antigen B7.

1991 • 1,662 citations

The B7–CD28 superfamily

2002 • 1,646 citations

Clonal Expansion Versus Functional Clonal Inactivation: A Costimulatory Signalling Pathway Determines the Outcome of T Cell Antigen Receptor Occupancy

1989 • 1,512 citations

The Central Role of CD4+ T Cells in the Antitumor Immune Response

1998 • 1,332 citations

A new member of the immunoglobulin superfamily—CTLA-4

1987 • 1,214 citations

Role of Bone Marrow-Derived Cells in Presenting MHC Class I-Restricted Tumor Antigens

1994 • 1,185 citations

Tumor Rejection After Direct Costimulation of CD8 ⁺ T Cells by B7-Transfected Melanoma Cells

1993 • 1,154 citations

Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4

1992 • 1,076 citations

Synergism of Cytotoxic T Lymphocyte–Associated Antigen 4 Blockade and Depletion of Cd25+ Regulatory T Cells in Antitumor Therapy Reveals Alternative Pathways for Suppression of Autoreactive Cytotoxic T Lymphocyte Responses

2001 • 1,033 citations

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

2001 • 1,032 citations

Combination Immunotherapy of B16 Melanoma Using Anti–Cytotoxic T Lymphocyte–Associated Antigen 4 (Ctla-4) and Granulocyte/Macrophage Colony-Stimulating Factor (Gm-Csf)-Producing Vaccines Induces Rejection of Subcutaneous and Metastatic Tumors Accompanied by Autoimmune Depigmentation

1999 • 1,000 citations

CTLA-4-Mediated Inhibition in Regulation of T Cell Responses: Mechanisms and Manipulation in Tumor Immunotherapy

2001 • 964 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

CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells.

1996 • 917 citations

The Duration of Antigenic Stimulation Determines the Fate of Naive and Effector T Cells

1998 • 890 citations

T-cell regulation by CD28 and CTLA-4

2001 • 857 citations

Massive Expansion of Antigen-Specific CD8+ T Cells during an Acute Virus Infection

1998 • 794 citations

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

1996 • 787 citations

Induction of Peripheral T Cell Tolerance In Vivo Requires CTLA-4 Engagement

1997 • 736 citations

T Cell Receptor Signaling Precedes Immunological Synapse Formation

2002 • 695 citations

Secretory lysosomes

2002 • 633 citations

Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes.

1992 • 592 citations

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

1996 • 583 citations

CD80 (B7-1) Binds Both CD28 and CTLA-4 with a Low Affinity and Very Fast Kinetics

1997 • 525 citations

A Kinetic Basis For T Cell Receptor Repertoire Selection during an Immune Response

1999 • 515 citations

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

2002 • 497 citations

T Cells Compete for Access to Antigen-Bearing Antigen-Presenting Cells

2000 • 423 citations

Combination immunotherapy of primary prostate cancer in a transgenic mouse model using CTLA-4 blockade.

2000 • 421 citations

T Cell Affinity Maturation by Selective Expansion during Infection

1999 • 420 citations

CTLA-4-Mediated Inhibition of Early Events of T Cell Proliferation

1999 • 412 citations

CTLA-4 Regulates Induction of Anergy In Vivo

2001 • 409 citations

Major Histocompatibility Complex Class II–Positive Cortical Epithelium Mediates the Selection of Cd4+25+ Immunoregulatory T Cells

2001 • 406 citations

Lymphoproliferation in CTLA-4–Deficient Mice Is Mediated by Costimulation-Dependent Activation of CD4 + T Cells

1997 • 405 citations

Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer

1997 • 383 citations

CTLA-4: a negative regulator of autoimmune disease.

1996 • 382 citations

CTLA-4 blockade synergizes with tumor-derived granulocyte– macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma

1998 • 375 citations

T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer

2001 • 373 citations

Vitiligo in Patients with Melanoma

1996 • 335 citations

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

1997 • 334 citations

Antigen-dependent clonal expansion of a trace population of antigen-specific CD4+ T cells in vivo is dependent on CD28 costimulation and inhibited by CTLA-4.

1995 • 323 citations

Characterization of CTLA-4 structure and expression on human T cells.

1993 • 319 citations

Elucidating the Autoimmune and Antitumor Effector Mechanisms of a Treatment Based on Cytotoxic T Lymphocyte Antigen-4 Blockade in Combination with a B16 Melanoma Vaccine

2001 • 307 citations

Cytotoxic T Lymphocyte–associated Antigen 4 (CTLA-4) Regulates the Unfolding of Autoimmune Diabetes

1998 • 295 citations

T-cell antigen CD28 interacts with the lipid kinase phosphatidylinositol 3-kinase by a cytoplasmic Tyr(P)-Met-Xaa-Met motif.

1994 • 291 citations

CTLA-4 Blockade Reverses CD8+ T Cell Tolerance to Tumor by a CD4+ T Cell– and IL-2-Dependent Mechanism

1999 • 287 citations

The specific direct interaction of helper T cells and antigen-presenting B cells.

1986 • 246 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

CTLA-4 blockade enhances clinical disease and cytokine production during experimental allergic encephalomyelitis.

1996 • 232 citations

Interaction of CTLA-4 with the clathrin-associated protein AP50 results in ligand-independent endocytosis that limits cell surface expression.

1997 • 225 citations

The Role of CTLA‐4 in the Regulation and Initiation of T‐Cell Responses

1996 • 208 citations

Enhanced induction of antitumor T-cell responses by cytotoxic T lymphocyte-associated molecule-4 blockade: the effect is manifested only at the restricted tumor-bearing stages.

1997 • 197 citations

Cytotoxic T Lymphocyte-associated Molecule-4, a High Avidity Receptor for CD80 and CD86, Contains an Intracellular Localization Motif in Its Cytoplasmic Tail

1995 • 189 citations

CTLA4Ig prevents lymphoproliferation and fatal multiorgan tissue destruction in CTLA-4-deficient mice.

1997 • 187 citations

Stimulation of CD28 triggers an association between CD28 and phosphatidylinositol 3-kinase in Jurkat T cells.

1994 • 183 citations

Peptide Dose, Affinity, and Time of Differentiation Can Contribute to the Th1/Th2 Cytokine Balance

1999 • 182 citations

Interaction of CTLA-4 with AP50, a clathrin-coated pit adaptor protein

1997 • 182 citations

B7-1 Engagement of Cytotoxic T Lymphocyte Antigen 4 Inhibits T Cell Activation in the Absence of CD28

1998 • 179 citations

The specific direct interaction of helper T cells and antigen-presenting B cells. II. Reorientation of the microtubule organizing center and reorganization of the membrane-associated cytoskeleton inside the bound helper T cells.

1987 • 177 citations

CTLA-4 binding to the lipid kinase phosphatidylinositol 3-kinase in T cells.

1995 • 161 citations

In vivoblockade of CTLA-4 enhances the priming of responsive T cells but fails to prevent the induction of tumor antigen-specific tolerance

1999 • 157 citations

B7-1 or B7-2 Is Required to Produce the Lymphoproliferative Phenotype in Mice Lacking Cytotoxic T Lymphocyte–associated Antigen 4 (CTLA-4)

1999 • 146 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

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

Blockade of CTLA-4 Enhances Host Resistance to the Intracellular Pathogen,Leishmania donovani

1998 • 135 citations

Superantigen responses and co-stimulation: CD28 and CTLA-4 have opposing effects on T cell expansion in vitro and in vivo

1996 • 132 citations

Selective Activation and Expansion of High-Affinity CD4+ T Cells in Resistant Mice upon Infection with Leishmania major

2000 • 130 citations

Realization of the therapeutic potential of CTLA-4 blockade in low-dose chemotherapy-treated tumor-bearing mice.

1998 • 129 citations

Structural mechanisms of costimulation

2002 • 129 citations

Interaction of the Cytoplasmic Tail of CTLA-4 (CD152) with a Clathrin-Associated Protein Is Negatively Regulated by Tyrosine Phosphorylation

1997 • 126 citations

CTLA-4 regulates cell cycle progression during a primary immune response

2002 • 122 citations

Cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates primary and secondary peptide-specific CD4⁺T cell responses

1999 • 115 citations

Protective Immunity to Nematode Infection Is Induced by CTLA-4 Blockade

1997 • 113 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

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

2001 • 105 citations

Specific blockade of CTLA-4/B7 interactions results in exacerbated clinical and histologic disease in an actively-induced model of experimental allergic encephalomyelitis

1997 • 102 citations

The Composition of a Primary T Cell Response Is Largely Determined by the Timing of Recruitment of Individual T Cell Clones

1999 • 86 citations

Antagonistic Roles for CTLA-4 and the Mammalian Target of Rapamycin in the Regulation of Clonal Anergy: Enhanced Cell Cycle Progression Promotes Recall Antigen Responsiveness

2001 • 85 citations

Cytotoxic T lymphocyte antigen-4 (CTLA-4) limits the expansion of encephalitogenic T cells in experimental autoimmune encephalomyelitis (EAE)-resistant BALB/c mice

2002 • 79 citations

Cytotoxic T lymphocyte antigen-4 (CTLA-4) regulates the size, reactivity, and function of a primed pool of CD4⁺T cells

2000 • 68 citations

Normal pathogen-specific immune responses mounted by CTLA-4-deficient T cells: a paradigm reconsidered

2001 • 58 citations

Absence of CTLA-4 Lowers the Activation Threshold of Primed CD8+ TCR-Transgenic T Cells: Lack of Correlation with Src Homology Domain 2-Containing Protein Tyrosine Phosphatase

2001 • 47 citations

Cytotoxic cells : basic mechanisms and medical applications

2000 • 34 citations

Augmentation of CTLA-4 expression by wortmannin: involvement of lysosomal sorting properties of CTLA-4

1999 • 17 citations