Recombinant Mouse Cytotoxic T-lymphocyte protein 4(Ctla4),partial (Active)

1. Immunogenic mouse neuroblastoma acquires adaptive immune resistance by up-regulating PD-L1 expression, whereas PD-L1 is of lesser consequence in nonimmunogenic neuroblastoma tumors. Combining PD-L1 checkpoint inhibition with whole tumor cell/anti-CTLA-4 vaccination enhanced tumor cell killing, cured mice with established tumors, and induced long-term immune memory (6 months). PMID: 29377881
2. the investigation of RANK and RANKL as possible novel immunotherapy targets in cancer is a rational approach. Here we have defined the mechanism of action of RANKL-RANK blockade in combination with anti-CTLA4, and provide insight into the combination efficacy observed in the case reports. PMID: 28634284
3. reveal a novel CTLA-4-mediated pathway to attenuate cytotoxic T-lymphocytes and indicate the importance of post-transcriptional mechanisms in the regulation of anti-tumor immune responses PMID: 28644433
4. The potential of the CTLA4 and G250 co-expression DNA vaccine. PMID: 28351777
5. Tregs were observed to regulate CD4(+), but not CD8(+), T cell infiltration into tumors through a CTLA-4/CD80 dependent mechanism. Disrupting CTLA-4 interaction with CD80 was sufficient to induce CD4 T cell infiltration into tumors. PMID: 28856392
6. These results suggest that CD44(+)CD117(+) T cells are stem cells and a specific T-cell phenotype that initially develops in the thymus, but they do not progress through DN3 and DN4 stages, lack a DP stage, and potently suppress T-cell proliferation and modulate the CTLA-4 pathway. PMID: 28279199
7. data suggest that increased expression of checkpoint blockade molecules PD-1 and CTLA-4 on donor T cells is not sufficient to prevent GvHD, and that cooperation between checkpoint blockade signaling by host cells and donor Tregs is necessary to limit GvHD in allo-HSCT recipients PMID: 28953925
8. Treg cells expand in both humans and mice in blood-stage malaria and interfere with conventional T helper cell responses and follicular T helper (TFH)-B cell interactions in germinal centers. Mechanistically, Treg cells function in a critical temporal window to impede protective immunity through cytotoxic-T-lymphocyte-associated protein-4 (CTLA-4). PMID: 28892065
9. CTLA-4 expressed by FOXP3(+) regulatory T cells prevents inflammatory tissue attack and not T-cell priming in arthritis. PMID: 28497863
10. results are consistent with a complex pathway in which CD28 is the primary driver of Treg proliferation and CTLA-4 functions as the main brake but is also dependent on TCR signals and interactions with CD80/CD86 PMID: 28053234
11. CTLA-4(+) microvesicles can competitively bind B7 costimulatory molecules on bystander dendritic cells, resulting in downregulation of B7 surface expression. PMID: 26979751
12. this study shows that miR-155 is modulated by a major dust mite allergen, Dermatophagoides farinae (Df1), and increases CD4+ T cell proliferation through the downregulation of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) expression PMID: 28110885
13. CTLA-4 regulates atherosclerosis by suppressing proatherogenic immune responses. PMID: 27055906
14. Data suggest enhanced clinical benefit from combining CTLA-4 antigen blockade with poxvirus-based active immunotherapy. PMID: 26961085
15. up-regulated expression correlates with the tolerogenic effect of syngeneic hematopoietic stem cell transplantation PMID: 26311302
16. Induced Treg Cells Augment the Th17-Mediated Intestinal Inflammatory Response in a CTLA4-Dependent Manner PMID: 26950218
17. CTLA-4 has a regulatory T cell-intrinsic role in limiting peripheral regulatory T cell expansion and activation, and in their capacity to control conventional T cells. PMID: 26371185
18. The Ctla4 SNP (e2_77A/G) does not alter diabetes susceptibility, but does control mRNA alternative splicing. PMID: 26450994
19. Sorafenib suppressed the expression of immunosuppressive factors in MDSCs. These data indicate that combination therapy of sorafenib and anti-CTLA-4 Ab may be effective in advanced kidney cancer patients. PMID: 25845968
20. The co-stimulatory molecule CTLA-4 mediates in vitro differentiation of iTreg cells. PMID: 25238105
21. The bullseye immunological synapse formation is mediated by CTLA4, and may negatively control T-cell activation as a suppressive synapse. PMID: 25287444
22. this study reports that regulatory T (Treg) cells orchestrate memory T cell quiescence by suppressing effector and proliferation programs through inhibitory receptor, cytotoxic- T-lymphocyte-associated protein-4 (CTLA-4). PMID: 26084026
23. Short-term blockade with anti-CTLA-4 antibody in wild-type mice is sufficient to elicit follicular helper T cell generation and germinal center development. The latter occurs in a CD28-dependent manner. PMID: 25548162
24. CTLA-4 and mTOR down-regulation cooperate during CD8+ T cell priming to promote memory formation and metabolic readiness. PMID: 25624453
25. role in Treg cell-mediated control of T follicular regulatory cell proliferation, germinal center formation,and of humoral immune responses PMID: 25526312
26. The study concludes that although the presence of CTLA4 plays a critical role in controlling homeostasis of T cells, its quantitative variation may impose diverse or even opposing effects on distinct lineages of T cells, an optimal sum of which is necessary for preservation of T cell immunity while suppressing tissue damage. PMID: 25246499
27. cardiomyocytes can express CD80; this expression pattern can resist CTL-mediated lysis through CTLA-4 pathway PMID: 24507064
28. Alternative splice forms of CTLA-4 induced by antisense mediated splice-switching influences autoimmune diabetes susceptibility in NOD mice. PMID: 24494586
29. CTLA4(apt) fused to a STAT3-targeting siRNA (CTLA4(apt)-STAT3 siRNA) resulted in internalization into tumor-associated CD8 T cells and silencing of STAT3, which activated tumor antigen-specific T cells in tumor models. PMID: 24892807
30. results show that CTLA-4 promotes Tc17 differentiation that results in robust Tc17 responses PMID: 24723371
31. These data suggest that effects associated with and mediated through Tyr201 of CTLA-4s intracellular domain are critical for Treg-cell function. PMID: 24648182
32. Our in vitro experiments revealed that IL-2 induced expression of CTLA-4 in mouse natural killer cells PMID: 24688023
33. These novel insights into the differential regulation of CTLA-4 coinhibition on CD4(+) T cells have implications for the immunomodulation of pathologic T cell responses during transplantation and autoimmunity. PMID: 24493820
34. SOCS3 interacts with CTLA-4 and negatively regulates CTLA-4 levels in T cells, providing a mechanistic explanation for the expansion of regulatory T cells in CD4-SOCS3 during experimental autoimmune uveitis. PMID: 24101549
35. This novel mechanism of CTLA-4lg immunotherapy may lead to an ideal anti-obesity/inflammation/insulin resistance agent. PMID: 23872146
36. Data show coexpression of PD-1 and CTLA-4 correlates with more severe dysfunction of tumor-specific CD8+ T cells. PMID: 23633484
37. Our results identify CTLA-4 as a key factor that regulates the composition of the Foxp3+ T-cell population in the intestine. PMID: 22910217
38. The soluble isoform of CTLA-4 is a regulator of T-cell responses. PMID: 23400950
39. The presence of the alternatively spliced 1/4 CTLA-4 isoform can further promote autoimmunity and autoimmune pathology in lupus-prone mice and suggests that altered splicing of CTLA4 contributes to the expression of autoimmune disease. PMID: 23203389
40. Li-CTLA-4 expressed at physiologic levels in the CTLA-4-sufficient NOD background suppresses autoimmunity; but, the functionality of the li-CTLA-4 isoform depends on the presence of the full-length molecule to alter effector T cell signaling. PMID: 23293354
41. CTLA-4 is expressed in the corticomedullary region of the thymus. Its absence alters the response of CD4(+)CD8(-) thymocytes to self-antigen recognition, which affects the quantity of the Treg cells and broadens the repertoire of peripheral T cells. PMID: 23267099
42. pathways by which cAMP regulates CTLA4 expression, focusing on transcriptional activation PMID: 23024062
43. Findings indicate that CTLA-4-negative regulation of conventional T cells (Tconvs) but not regulatory T cells (Tregs) in immune responses. PMID: 23047820
44. direct evidence that CTLA4 inhibits spontaneous tumor development PMID: 22777737
45. CTLA-4 on normal effector CD4-positive T cells completely abrogates the dramatically increased expansion normally experienced by their CTLA-4-deficient counterparts. PMID: 22753941
46. a potential new role for CTLA-4 in Treg differentiation PMID: 22337882
47. the importance of intracellular localization for CTLA-4 protein function and reveal that CTLA-4 protein externalization imparts suppressor function to both regulatory and conventional CD4(+) T cells. PMID: 22403258
48. boosting CD152 or its down-stream signal transduction could aid therapies aimed at sensitizing T lymphocytes for optimal migration, thus contributing to a precise and effective immune response. PMID: 22412835
49. The expression of CTLA-4 and PD-1 on T cells correlates with the extent of proinflammatory responses induced during Plasmodium berghei infection, being higher in C57BL/6 than in BALB/c mice. PMID: 22319445
50. CTLA4-Ig may promote neuronal differentiation during the treatment of neurological diseases with cell replacement therapy PMID: 22155494
51. the function of the 1/4CTLA-4 isoform is distinct from that of CTLA-4 in that it enhances T cell activation and promotes autoimmunity rather than inhibiting immune responses. PMID: 22124121
52. Studies indicate that CTLA-4 and PD-1 blockade augmented antitumor immunity. PMID: 21700764
53. Data for and against the T cell-intrinsic and -extrinsic functions of CTLA4 are presented (Review) PMID: 22116087
54. The role of CTLA4 as an inhibitory co-signaling molecule in activated T lymphocytes is reviewed. Review. PMID: 22027421
55. T-cell co-inhibitory blockade combined with alphaCTLA-4 and active co-stimulation with alpha4-1BB promotes rejection of B16 melanoma in with a vaccine; KLRG1 is a useful marker for monitoring the anti-tumor immune response elicited by this therapy PMID: 21559358
56. CTLA4 signal is required for T cell tolerance in the context of acute GVHD after myeloablative allogeneic bone marrow transplantation. PMID: 21447398
57. loss of sCTLA-4 impairs the function of Treg cells and compromises immune regulation, with the notable consequence of increasing the risk of autoimmunity in the NOD background. PMID: 21602513
58. This study shows that the quantity of memory CD4+ T cells generated during an immune response is regulated independently of CTLA-4 signaling but CD4+ T cells are strongly influenced by CTLA-4. PMID: 21478403
59. the blockade of CTLA-4 did not unlock the stability of Treg cells PMID: 21418778
60. Foxp3(+) Treg cell-mediated protection was dependent upon CTLA-4 but not IL-10. PMID: 21170302
61. study shows CTLA-4 can capture its ligands (CD80, CD86)from opposing cells by trans-endocytosis; data reveal mechanism of immune regulation in which CTLA-4 acts as an effector molecule to inhibit CD28 costimulation by cell-extrinsic depletion of ligands PMID: 21474713
62. The CTLA-4-mediated suppression was demonstrated by the in vitro anergy induction in regulatory T cells constitutively expressing CTLA-4. PMID: 20870175
63. The interaction of CTLA-4 and B7 inhibits T helper cell type (Th)17 differentiation in vitro and in vivo and suppresses Th17-mediated autoimmunity. Blocking the CTLA4-B7 interaction potentiates Th17 cell differentiation in vitro and in vivo. PMID: 20601598
64. Abnormal expression of CD28 and CTLA4 in T cells was observed in mice with aplastic anemia. PMID: 16463658
65. In a murine model of acute lung injury (ALI), analysis of lipopolysaccharide-induced CD4-positive T helper cell pathways reveals increased CTLA4 expression contributing to experimental ALI. PMID: 20385880
66. SP-D decreases allergen responses, an effect that may be mediated by increase of CTLA4 in T cells. PMID: 20435925
67. dendritic cell directed enhanced CTLA-4 engagement upon pancreatic beta cell Ag presentation results in the suppression of autoreactive T cell response in NOD mice PMID: 20483724
68. CTLA-4 mediates signals via the activation of the ubiquitin ligase Itch PMID: 20417562
69. blockage does not abrogate the protective effect of regulatory T cells in a pregnancy model PMID: 19811462
70. results suggest that combination blockade of the PD-1/PD-L1- and CTLA-4-negative costimulatory pathways allows tumor-specific T cells that would otherwise be inactivated to continue to expand and carry out effector functions PMID: 20160101
71. show here that lack of CTLA-4 in regulatory T cells leads to aberrant activation and expansion of conventional T cells. PMID: 20080649
72. CTLA-4 pathway exerts its major effects on T cell immune responses via regulation of the cell cycle. PMID: 11807776
73. The B7-CD28/CTLA-4 costimulatory pathway has a dominant role in regulating T-cell activation. Antagonists enable graft survival and suppress autoimmunity. PMID: 11826754
74. CTLA-4 contributes to the maintenance of peripheral T cell tolerance to self antigens. PMID: 11867713
75. Negative effect of CTLA-4 on induction of T-cell immunity in vivo to B7-1+, but not B7-2+, murine myelogenous leukemia. PMID: 11877291
76. CTLA-4 is required to maintain the unresponsive state of the tolerized T cells upon antigenic stimulation under inflammatory conditions and, therefore, have important implications for therapeutic regulation of autoimmune disease. PMID: 11920563
77. B7-CTLA4 interaction promotes cognate destruction of tumor cells by cytotoxic T lymphocytes in vivo. PMID: 11929778
78. A three-lysine motif in the juxtamembrane portion of the CTLA-4 cytoplasmic tail has been identified as the region of binding and down-regulation by the regulatory subunit of protein phosphatase 2A (PP2A). PMID: 11994459
79. Expression of a mutant membrane-bound single-chain anti-CTLA-4 antibody on allogeneic tumor cells results in suppression of T cell activation in vivo and prevents rejection of the CTLA-4-competent allogeneic tumor. PMID: 12097362
80. Local expresssion in a pancreatic beta-cell line suppresses accelerated graft rejection response induced by donor-specific transfusion PMID: 12107727
81. Re-establishing peripheral tolerance in the absence of CTLA-4: complementation by wild-type T cells points to an indirect role for CTLA-4. PMID: 12165509
82. CTLA-4 expression restricts pathogen-specific T cell responses and prevents immune pathology during infection with Plasmodium berghei. PMID: 12193697
83. In T cells deficient in CD80 and CD86 (double knockout), or CTLA-4, CD80, and CD86 (triple knockout), CTLA-4 ligation up-regulates and sustains c-Jun N-terminal kinase activation, while inhibiting extracellular signal-regulated kinase activity. PMID: 12244135
84. CTLA-4 negative signaling plays a critical role in regulating alloimmunity, especially under conditions where the alloreactive T cell clone size is relatively small. PMID: 12244168
85. with B7 antigen, is essential for generating regulatory cells after intratracheal delivery of alloantigen in mice PMID: 12352894
86. CTLA-4 expression on antigen-specific cells is required for oral tolerance. PMID: 12355454
87. CTLA-4-Ig regulates cytokine-dependent tryptophan catabolism in B7-expressing dendritic cells, suggesting that tryptophan catabolism modulation is the way CTLA-4 functions in vivo & that CTLA-4 acts as a ligand for signal-transducing B7 receptors. PMID: 12368911
88. Role of CTLA4 in enhancing cell-cycle progression and survival of CD4(+) T lymphocytes after activation. PMID: 12429713
89. CTLA-4 may preferentially dampen pathologic immune responses to self proteins while permitting protective immunity to foreign agents. PMID: 12444125
90. In a study of germinal center responses in mice with compromised ability to signal through T cell CTLA-4, a critical role is shown for CTLA-4 in down-regulating T cell help for germinal center B cells. PMID: 12496387
91. Negative regulation of T cell receptor-lipid raft interaction by cytotoxic T lymphocyte-associated antigen 4. PMID: 12515820
92. CTLA-4 has a critical role in T cell differentiation PMID: 12524538
93. role of CD28(SDYMNM) and CTLA-4(GVYVKM) motifs in distinguishing positive versus negative coreceptor signaling in T cells PMID: 12525576
94. Anti-CD28 has a potent adjuvant effect on the antibody response to soluble antigens mediated through CTLA-4 by-pass PMID: 12594842
95. Inhibition of dipeptidylpeptidase IV (DPP IV, CD26) activity modulates surface expression of this protein in stress-induced abortion. PMID: 12675235
96. In the mouse model of type 1 diabetes, susceptibility was also associated with variation in CTLA-4 gene splicing with reduced production of a splice form encoding a molecule lacking the CD80/CD86 ligand-binding domain PMID: 12724780
97. Engagement of CTLA-4 inhibits deletion of superantigen-mediated deletion; in the absence of CTLA-4, TCR V beta 3+ thymocytes are more readily deleted. PMID: 12759417
98. A signal through CTLA4, rather than through CD28, plays an important role in the induction of hyporesponsiveness by intratracheal delivery of alloantigen in this model. PMID: 12777848
99. BTLA is a third inhibitory receptor on T lymphocytes with similarities to cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1). PMID: 12796776
100. Iris pigment epithelial cells constitutively express cell surface CD86, which enables the cells to contact inhibit T cells via direct interaction with CTLA-4. PMID: 12835481

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KEGG: mmu:12477

STRING: 10090.ENSMUSP00000027164

UniGene: Mm.390