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  • target
  • Such an exercise may ultimately help us to design immunotherapeutic agents that target CTLA-4. (uwo.ca)
  • Function
  • A Molecular Perspective of CTLA-4 Function" by Wendy A. Teft, Mark G. Kirchhof et al. (uwo.ca)
  • ligand
  • The nature of TCR-ligand interaction that initiates the lymphoproliferation and the extent to which individual naive CD4 + T cells become dysregulated by the absence of CTLA-4 in vivo is unknown. (pnas.org)
  • CD86
  • We used a neutralizing antibody to block CTLA-4 interaction with its ligands CD80 and CD86 during infection of mice with the nematode, Nippostrongylus brasiliensis. (nih.gov)
  • 2. Administration of anti-LFA-1/ICAM-1, anti-VLA-4/VCAM-1, anti-CD2/CD48, or anti-CD80/CD86 mAbs could induce cardiac, bowel, or plancreatic islet allograft tolerance. (nii.ac.jp)
  • 4. Lethal GVHD after bone marrow transplantation was prevented by the administration of anti-CD80/CD86 mAbs. (nii.ac.jp)
  • cytokine
  • The absence of CTLA-4 also augments the responder frequency of cytokine-secreting AND TCR + RAG −/− T cells. (pnas.org)
  • Fig. 2 b) but it is interesting that in this lymph node peak cytokine production occurred at the same time in control and anti-CTLA-4- treated mice. (nih.gov)
  • Increased cytokine production from this lymph node reflected increased IL-4 and IL-5 production only as total mesenteric lymph node cell numbers were not significantly different between groups (data not shown). (nih.gov)
  • We show that ICOS + T cells comprised a population of Th1 cytokine producing and tumor antigen-specific effector cells. (aacrjournals.org)
  • transgenic mouse
  • The role of CTLA-4 in regulating homeostasis and antigen reactivity of CD8 + T cells has been examined in three different MHC class I-restricted TCR transgenic mouse strains ( 21 - 23 ). (pnas.org)
  • autoimmune
  • Particular genotypes of the locus encoding the CTLA-4 glycoprotein have been associated with susceptibility to various autoimmune diseases. (semanticscholar.org)
  • Rejection of B16-BL6 or B16-F10 as a result of treatment with anti-CTLA-4 and GM-CSF-producing vaccines causes autoimmune skin and hair depigmentation. (nih.gov)
  • However, in its day-to-day activities, CTLA-4 prevents autoimmune targeting of tissues ( 2 ), though the precise mechanism of action and critical controls influencing CTLA-4 function are still emerging. (sciencemag.org)
  • The clinical evidence strongly suggests that the prostate cancer subjects developed autoimmune hypophysitis as a consequence of anti-CTLA-4 treatment. (springer.com)
  • immunity
  • Since the cells and the molecules of the immune system are a fundamental component of the tumor microenvironment (TME), cancer immunotherapy has emerged as a powerful new therapeutic approach to boost antitumor immunity response ( 4 ). (frontiersin.org)
  • tumors
  • While many of these therapies have offered substantial benefit for eradication of primary tumors, the incidence of disease relapse is still a commonly encountered problem that results from residual malignant cells and/or tumor metastases [ 3 , 4 ]. (jcancer.org)
  • clinical outcome
  • To determine if CD4 + ICOS hi T cells could be a correlative marker for clinical outcome after treatment with anti-CTLA-4, a cohort of metastatic melanoma patients was studied retrospectively for frequency of CD4 + ICOS hi T cells and survival. (aacrjournals.org)
  • Immunological
  • We previously conducted a presurgical clinical trial to obtain tumor tissues and peripheral blood for immunological studies after patients were treated with anti-CTLA-4. (aacrjournals.org)
  • enhances
  • Treatment with anti-CTLA-4 greatly enhances IL-5 production in lymph nodes draining the sites of infection with Nb. (nih.gov)
  • mice
  • CTLA-4-deficient mice develop a fatal lymphoproliferative disorder, characterized by polyclonal expansion of peripheral lymphocytes. (pnas.org)
  • CTLA-4-deficient mice die at 3-4 weeks of age as a result of a lymphoproliferative disorder caused by polyclonal T cell expansion ( 12 - 14 ). (pnas.org)
  • Based on the phenotype of the CTLA-4 −/− mice, we proposed ( 15 , 16 ) that CTLA-4 may provide an inhibitory signal that prevents CD4 + T cell activation during the continuous interaction of TCR and MHC that is shown to be required for T cell survival ( 17 - 21 ). (pnas.org)
  • C57BL/6 mice were inoculated i.p. with 1,000 Nb L3 larvae and treated with control hamster IgG (open squares) or hamster anti-mouse CTLA-4 mAb (filled squares) at 1 mg/week beginning at day 0. (nih.gov)
  • We found that anti-CTLA-4 mAb treatment induced a profound 20-fold increase in IL-5 production (Fig. 1 a) and a massive 40-fold increase in IL-4 production (Fig. 2 a) from the draining mediastinal lymph node at day 6 after infection compared to mice given control antibody. (nih.gov)
  • The mediastinal lymph node obtained from mice given anti-CTLA-4 mAb had nearly fourfold more lymphocytes 6 d after infection than control mice (Fig. 3). (nih.gov)
  • To determine whether the ICOS/ICOSL pathway might play a causal role in the antitumor effects mediated by anti-CTLA-4, we conducted studies in ICOS-sufficient and ICOS-deficient mice bearing B16/BL6 melanoma. (aacrjournals.org)
  • vivo
  • CTLA-4 signaling has been implicated in tolerance induction in vivo and may also augment suppressor CD4+ T-cell activity, thereby downregulating the immune response ( 7 - 10 ). (aacrjournals.org)
  • modulate
  • rather, accumulating evidence indicates that CTLA-4 may directly modulate proximal TCR signaling ( 5 - 11 ). (pnas.org)
  • immunogenic
  • We report here a strategy using the transgenic adenocarcinoma of mouse prostate (TRAMP) model, which allows for the functional identification of immunogenic prostate tumor antigens with relevance for human immunotherapy. (nih.gov)
  • outcome
  • These cases highlight the importance of early screening and treatment for hypopituitarism in all subjects undergoing treatment with anti-CTLA-4 therapy to prevent a potentially fatal outcome from secondary adrenal insufficiency, a readily treatable disease. (springer.com)
  • lymphoproliferation
  • Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH (1995) Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. (springer.com)
  • mAbs
  • 5. Administration of anti-LFA-1/ICAM-1 mAbs not only prevented mouse or rat collagen-induced arthritis but also induced resistancy against the subsequent challenge with the same antigen. (nii.ac.jp)
  • therapeutic
  • Our findings establish that the ICOS/ICOSL pathway is necessary for the optimal therapeutic effect of anti-CTLA-4, thus implicating this pathway as a target for future combinatorial strategies to improve the efficacy of anti-CTLA-4 therapy. (aacrjournals.org)
  • prostate cancer
  • Discovery of immunologically relevant antigens in prostate cancer forms the basis for developing more potent active immunotherapy. (nih.gov)