Search results for "T-Lymphocyte Subsets"
showing 10 items of 172 documents
Genetic evolution of T-cell resistance in the course of melanoma progression
2014
Abstract Purpose: CD8+ T lymphocytes can kill autologous melanoma cells, but their activity is impaired when poorly immunogenic tumor phenotypes evolve in the course of disease progression. Here, we analyzed three consecutive melanoma lesions obtained within one year of developing stage IV disease for their recognition by autologous T cells. Experimental Design: One skin (Ma-Mel-48a) and two lymph node (Ma-Mel-48b, Ma-Mel-48c) metastases were analyzed for T-cell infiltration. Melanoma cell lines established from the respective lesions were characterized, determining the T-cell–stimulatory capacity, expression of surface molecules involved in T-cell activation, and specific genetic alteratio…
Functional TCR Retrieval from Single Antigen-Specific Human T Cells Reveals Multiple Novel Epitopes
2014
Abstract The determination of the epitope specificity of disease-associated T-cell responses is relevant for the development of biomarkers and targeted immunotherapies against cancer, autoimmune, and infectious diseases. The lack of known T-cell epitopes and corresponding T-cell receptors (TCR) for novel antigens hinders the efficient development and monitoring of new therapies. We developed an integrated approach for the systematic retrieval and functional characterization of TCRs from single antigen-reactive T cells that includes the identification of epitope specificity. This is accomplished through the rapid cloning of full-length TCR-α and TCR-β chains directly from single antigen-spec…
A specific CD4 epitope bound by tregalizumab mediates activation of regulatory T cells by a unique signaling pathway
2014
CD4(+)CD25(+) regulatory T cells (Tregs) represent a specialized subpopulation of T cells, which are essential for maintaining peripheral tolerance and preventing autoimmunity. The immunomodulatory effects of Tregs depend on their activation status. Here we show that, in contrast to conventional anti-CD4 monoclonal antibodies (mAbs), the humanized CD4-specific monoclonal antibody tregalizumab (BT-061) is able to selectively activate the suppressive properties of Tregs in vitro. BT-061 activates Tregs by binding to CD4 and activation of signaling downstream pathways. The specific functionality of BT-061 may be explained by the recognition of a unique, conformational epitope on domain 2 of th…
Th9 cells, new players in adaptive immunity.
2014
Upon antigen-specific stimulation, naive CD4⁺ T cells have the potential to differentiate into various T helper (Th) cell subsets. Earlier models of Th cell differentiation focused on IFN-γ-producing Th1 cells and IL-4-secreting Th2 cells. The discovery of additional CD4⁺ Th cell subsets has extended our understanding of Th cell differentiation beyond this dichotomy. Among these is the recently described Th9 cell subset, which preferentially produces interleukin (IL)-9. Here, we review the latest developments in Th9 cell development and differentiation, focusing on contributing environmental signals, and discuss potential physiological and pathophysiological functions of these cells. We des…
Understanding the Role of T Cells in CNS Homeostasis.
2015
T cells within the central nervous system (CNS) have been generally considered pathogenic, especially in the context of neuroinflammatory disease. However, recent findings have revealed varied functions for T cells in the healthy CNS, as well as more complex roles for these cells in infection and injury than previously appreciated. Here we review evidence indicating important roles for different T cell subsets in the maintenance of CNS homeostasis. We examine the contribution of T cells in limiting inflammation and damage upon CNS injury, infection, and in neurodegeneration, and discuss the current understanding of the cellular and molecular mechanisms involved. Insight into these processes…
Cytokines in Colitis-Associated Cancer: Potential Drug Targets?
2008
In inflammatory bowel disease (IBD), such as UC and CD, the development of colorectal carcinoma can be initiated through chronic inflammation, depending on the duration and severity of the disease. Growing evidence supports a role for various cytokines, released by epithelial and immune cells, in the pathogenesis of colitis associated cancer (CAC). For instance, TNF-alpha has been recently shown to promote tumor development in experimental colitis. Due to its role in the pathogenesis of IBD, TNF-alpha blockade has become one of the cornerstones of IBD therapy. Thus, anti-TNF-alpha strategies could also provide effective anti-tumor therapies. TGF-beta has been shown to attenuate an anti-tumo…
γδ T cells as a potential tool in colon cancer immunotherapy
2014
γδ T cells are capable of recognizing tumor cells and exert potent cellular cytotoxicity against a large range of tumors, including colon cancer. However, tumors utilize numerous strategies to escape recognition or killing by patrolling γδ T cells, such a downregulation of NKG2D ligands, MICA/B and ULBPs. Therefore, the combined upregulation of T-cell receptorand NKG2D ligands on tumor cells and induction of NKG2D expression on γδ T cells may greatly enhance tumor killing and unlock the functions of γδ T cells. Here, we briefly review current data on the mechanisms of γδ T-cell recognition and killing of colon cancer cells and propose that γδ T cells may represent a promising target for the…
Combining dasatinib with dexamethasone long-term leads to maintenance of antiviral and antileukemia specific cytotoxic T cell responses in vitro
2012
Maintaining graft versus leukemia (GvL) and antivirus responses of cytotoxic T cells (CTLs) while suppressing graft-versus-host disease (GvHD) remains a challenge after allogeneic bone marrow transplantation. Clinical observations indicate that combining glucocorticoids with multi-tyrosine-kinase inhibitors could be a successful therapeutic approach. We and others have shown that the BCR-ABL/SRC kinase inhibitor dasatinib may enhance or suppress T cells in vitro. In this report, we evaluated combination effects of dasatinib and dexamethasone on CD3 + and virus-specific CD8 + T cells directly ex vivo and on antigen-specific leukemia-reactive and alloreactive CD8 + T cell clones. Functional o…
Homing and memory patterns of human gammadelta T cells in physiopathological situations.
2004
Vgamma9Vdelta2 are a heterogeneous population of T cells and comprise distinct naive, memory and effector populations that can be distinguished on the basis of surface marker expression and effector functions. We review here these recently studied features of Vgamma9Vdelta2 T lymphocyte biology and the roles they play in infectious and autoimmune diseases.
MAPK3 deficiency drives autoimmunity via DC arming.
2010
DC are professional APC that instruct T cells during the inflammatory course of EAE. We have previously shown that MAPK3 (Erk1) is important for the induction of T-cell anergy. Our goal was to determine the influence of MAPK3 on the capacity of DC to arm T-cell responses in autoimmunity. We report that DC from Mapk3(-/-) mice have a significantly higher membrane expression of CD86 and MHC-II and--when loaded with the myelin oligodendrocyte glycoprotein--show a superior capacity to prime naive T cells towards an inflammatory phenotype than Mapk3(+/+) DC. Nonetheless and as previously described, Mapk3(-/-) mice were only slightly but not significantly more susceptible to myelin oligodendrocyt…