Search results for "IL-2"

Human CD8+ memory and EBV-specific T cells show low alloreactivity in vitro and in CD34+ stem cell–engrafted NOD/SCID/IL-2Rγcnull mice

2013

Current strategies in cellular immunotherapy of cancer and viral infections include the adoptive transfer of T cell receptor (TCR) and chimeric antigen receptor engineered T cells. When using transient RNA expression systems in clinical studies, multiple infusions with receptor-redirected T cells appear necessary. However, in allogeneic hematopoietic stem-cell transplantation, repeated transfer of donor-derived T cells increases the risk of alloreactive graft-versus-host disease. We investigated naive-derived (T N ), memory-derived (T M ), and Epstein Barr virus-specific (T EBV ) CD8 + T cell subsets for alloreactivity upon redirection with RNA encoding a cytomegalovirus-specific model TCR.…

Allergen-specific immune deviation from a T H2 to a T H1 response induced by dendritic cells and collagen type I

1999

Background: Atopy and IgE production are associated with enhanced allergen-specific TH2 responses. Therefore a causative treatment may result from the deviation of this T H2dominated immune response toward a TH1 response. Objective: This study was carried out to analyze whether dendritic cells, the most potent antigen-presenting cells that are also known to induce antigen-specific T H1 responses, are suitable for therapy of atopic diseases by shifting the allergen-specific TH2 response toward a TH1 response. Methods: Monocyte-derived dendritic cells were used to present allergens in vitro to autologous CD4 + T cells of allergic persons. Because collagen type I activates dendritic cells and …

IL-23R determines susceptibility in Crohn's disease in a Mediterranean area

2009

2004

Autoimmune inflammation, such as in rheumatoid arthritis, is characterized by activated Th1 cells without sufficient Th2 differentiation that might downmodulate the chronic immune response. Delineation of the mechanisms that control T-cell differentiation is therefore of major importance for the understanding of the pathogenesis of autoimmune diseases. The transcription factor GATA-3 has been implicated in regulating Th2 cell differentiation in murine T cells in vitro, but its role in vivo and, in particular, in human T-cell differentiation is currently unknown. To dissect the role of GATA-3 in human T-cell differentiation and T-cell-mediated effector functions, we used the unique opportuni…

Suppressor activity of anergic T cells induced by IL-10-treated human dendritic cells: association with IL-2- and CTLA-4-dependent G1 arrest of the c…

2003

We have previously shown that human IL-10-treated dendritic cells (DC) induce an antigen-specific anergy in CD4+ T lymphocytes. These anergic T cells are characterized by an inhibited proliferation, a reduced production of IL-2, and additionally display antigen-specific suppressor activity. In this study we investigated the mechanisms underlying the anergic state and regulatory function of these T cells. We did not observe enhanced rates of programmed cell death of anergic CD4+ suppressor T cells compared to T cells stimulated with mature DC. Cell cycle analysis by DNA staining and Western blot experiments revealed an arrest of anergic CD4+ T suppressor cells in the G1 phase. High levels of…

Tuning tumor-specific T-cell activation: a matter of costimulation?

2002

Abstract The stimulation of a specific antitumor immune response, involving the recruitment of T cells and induction of T-cell effector functions, is an attractive possibility for cancer immunotherapy. In the past few years, advances in our understanding of the mechanisms of T-cell activation and costimulation have provided the basis for strategies to enhance antitumor immunity and break tolerance. These strategies include the equipment of tumor cells with costimulatory molecules such as B7, blockade of inhibitory signals on T cells (e.g. through cytotoxic T-lymphocyte antigen 4) and grafting of T cells with antigen-triggered, recombinant costimulatory receptors. Combining antigen-triggered…

Identification and Functional Characterization of Human Cd4+Cd25+ T Cells with Regulatory Properties Isolated from Peripheral Blood

2001

A subpopulation of peripheral human CD4(+)CD25(+) T cells that expresses CD45RO, histocompatibility leukocyte antigen DR, and intracellular cytotoxic T lymphocyte-associated antigen (CTLA) 4 does not expand after stimulation and markedly suppresses the expansion of conventional T cells in a contact-dependent manner. After activation, CD4(+)CD25(+) T cells express CTLA-4 on the surface detectable for several weeks. These cells show a G1/G0 cell cycle arrest and no production of interleukin (IL)-2, IL-4, or interferon (IFN)-gamma on either protein or mRNA levels. The anergic state of CD4(+)CD25(+) T cells is not reversible by the addition of anti-CD28, anti-CTLA-4, anti-transforming growth fa…

Human CD4+CD25+ T cells derived from the majority of atopic donors are able to suppress TH1 and TH2 cytokine production

2003

Abstract Background: Recently, it has been established that CD4 + CD25 + T cells with regulatory capacity are present in human peripheral blood, inhibiting allogeneic proliferation and cytokine production of preactivated CD4 + CD25 − respond-er T cells. Objective: The aim of this study was to analyze in an allergen-specific setting whether such regulatory CD4 + CD25 + T cells also exist and function normally in atopic individuals, especially concerning the inhibition of T H 2 cytokines. Methods: For this purpose, CD4 + CD25 − or CD4 + CD25 + T cells from donors allergic to grass or birch pollen (mainly with rhinitis) or from healthy nonatopic donors were stimulated in the presence of autolo…

Costimulatory signalling potential of murine MHC class II‐positive T‐clone cells

1996

Activated human and rat T cells as well as mouse T-cell clones have been reported to synthesize and express major histocompatibility complex (MHC) class II molecules. However, the capacity of class II+ antigen (Ag) presenting T cells to induce proliferation of Ag-specific cloned T cells has been controversial. We analysed whether the failure of some T-cell clones to proliferate in response to Ag presented by class II+ T cells is because of a lack of costimulatory cytokine production by the antigen-presenting cells (APC). As a model system the mouse class II+ cloned BI/O4.1 T cells were used as APC in order to activate the T cell clone KIII5. This T-helper 1 (Th1) type, GAT (synthetic copoly…

Inhibition of human allergic T-helper type 2 immune responses by induced regulatory T cells requires the combination of interleukin-10-treated dendri…

2006

Summary Background In grass pollen-allergic individuals, T cell anergy can be induced by IL-10-treated dendritic cells (IL-10-DC) resulting in the suppression of T helper type 1 (Th1) as well as Th2 cells. This study was performed to analyse whether such IL-10-DC-treated T cells are able to act as regulatory T cells (Treg) suppressing the function of other T cells in the periphery. As transforming growth factor (TGF)-β is also a potential inducer of Treg, we additionally analysed the inhibitory capacity of TGF-β-treated T cells in this system. Materials and Methods Freshly isolated CD4+ or CD4+CD25− T cells from grass pollen-allergic donors were stimulated with autologous mature monocyte-de…