Search results for "Interleukin 21"
showing 10 items of 178 documents
Co-development of naive CD4+ cells towards T helper Type 1 or T helper type 2 cells induced by a combination of IL.-12 and IL-4
1997
Abstract Cytokines were found to play a key role in Th cell differentiation. Among them IL-12 was shown to be a potent differentiation factor for Th1 cells, whereas IL-4 is the only known cytokine that promotes the development of Th2 cells. Upon addition of comparable amounts of IL-4 and IL-12 to a primary culture of naive CD4 + T cells activated by immobilized anti-CD3 mAb, it was found that the Th1-inducing capacity of IL-12 is dominated by the Th2-promoting effect of IL-4. However, high amounts of IL-12 (10,000 U/ml) in combination with low amounts of IL-4 (100 U/ml) led to the development of a Th cell population that, upon rechallenge, showed a substantial secondary IFN-γ (Th1 cytokine)…
Deficiency in the Transcription Factor Interferon Regulatory Factor (Irf)-2 Leads to Severely Compromised Development of Natural Killer and T Helper …
2000
Interferon (IFN) regulatory factor (IRF)-2 was originally described as an antagonist of IRF-1–mediated transcriptional regulation of IFN-inducible genes. IRF-1−/− mice exhibit defective T helper type 1 (Th1) cell differentiation. We have used experimental leishmaniasis to show that, like IRF-1−/− mice, IRF-2−/− mice are susceptible to Leishmania major infection due to a defect in Th1 differentiation. Natural killer (NK) cell development is compromised in both IRF-1−/− and IRF-2−/− mice, but the underlying mechanism differs. NK (but not NK+ T) cell numbers are decreased in IRF-2−/− mice, and the NK cells that are present are immature in phenotype. Therefore, like IRF-1, IRF-2 is required for…
Development of hapten-induced IL-4-producing CD4+ T lymphocytes requires early IL-4 production by alphabeta T lymphocytes carrying invariant V(alpha)…
1998
This paper investigates the mechanisms responsible for the generation of IL-4-producing CD4+ T cells during contact sensitization with the hapten trinitrochlorobenzene (TNCB). Lymph node cells taken 1 day after immunization spontaneously released IL-4 while lymph node cells taken 2 and 3 days after immunization did not produce IL-4. A second wave of IL-4 production that was both antigen-specific and MHC class II (I-A)-restricted was observed 4 days after immunization. The spontaneous release of IL-4 at day 1 was due to the alphabeta+ double-negative (CD4- CD8-) T lymphocytes that also expressed NK1.1 and showed V(alpha)14 rearrangement, while alphabeta+ CD4+ T lymphocytes were the source of…
The Transcription Factor T-bet Regulates Mucosal T Cell Activation in Experimental Colitis and Crohn's Disease
2002
The balance between pro and antiinflammatory cytokines secreted by T cells regulates both the initiation and perpetuation of inflammatory bowel diseases (IBD). In particular, the balance between interferon (IFN)-gamma/interleukin (IL)-4 and transforming growth factor (TGF)-beta activity controls chronic intestinal inflammation. However, the molecular pathways that evoke these responses are not well understood. Here, we describe a critical role for the transcription factor T-bet in controlling the mucosal cytokine balance and clinical disease. We studied the expression and function of T-bet in patients with IBD and in mucosal T cells in various T helper (Th)1- and Th2-mediated animal models …
Cellular and humoral immune responses against autoreactive T cells in multiple sclerosis patients after T cell vaccination.
1999
Myelin basic protein (MBP)-reactive T cells may play an important role in the autoimmune pathogenesis of multiple sclerosis (MS). MBP-reactive T cells can be specifically targeted by T cell vaccination, a procedure whereby MS patients are immunized with attenuated autologous MBP reactive T cells. T cell vaccination induces immune responses to the vaccine cells together with a depletion of MBP reactive T cells. Forty-nine MS patients were treated with T cell vaccination in an extended phase I trial to study the safety, immune responses and clinical effects of T cell vaccination. In the present paper the immune responses towards the vaccine cells were characterized. Substantial long-term in v…
Induction of CD4+/CD25+ regulatory T cells by targeting of antigens to immature dendritic cells
2003
AbstractCoupling of ovalbumin (OVA) to anti–DEC-205 monoclonal antibody (mAb) (αDEC) induced the proliferation of OVA-specific T cells in vivo. Expansion was short-lived, caused by dendritic cells (DCs), and rendered T cells anergic thereafter. Phenotypic analysis revealed the induction of CD25+/CTLA-4+ T cells suppressing proliferation and interleukin-2 (IL-2) production of effector CD4+ T cells. The findings were supported by 2 disease models: (1) CD4+ T-cell–mediated hypersensitivity reactions were suppressed by the injection of αDEC-OVA and (2) the application of hapten-coupled αDEC-205 reduced CD8+ T-cell–mediated allergic reactions. Thus, targeting of antigens to immature DCs through …
Chemokines enhance immunity by guiding naive CD8+ T cells to sites of CD4+ T cell-dendritic cell interaction.
2005
CD8+ T cells have a crucial role in resistance to pathogens and can kill malignant cells; however, some critical functions of these lymphocytes depend on helper activity provided by a distinct population of CD4+ T cells. Cooperation between these lymphocyte subsets involves recognition of antigens co-presented by the same dendritic cell, but the frequencies of such antigen-bearing cells early in an infection and of the relevant naive T cells are both low. This suggests that an active mechanism facilitates the necessary cell-cell associations. Here we demonstrate that after immunization but before antigen recognition, naive CD8+ T cells in immunogen-draining lymph nodes upregulate the chemok…
Alloreactive and leukemia-reactive T cells are preferentially derived from naive precursors in healthy donors: implications for immunotherapy with me…
2011
Background HLA mismatch antigens are major targets of alloreactive T cells in HLA-incompatible stem-cell transplantation, which can trigger severe graft- versus -host disease and reduce survival in transplant recipients. Our objective was to identify T-cell subsets with reduced in vitro reactivity to allogeneic HLA antigens. Design and Methods We sorted CD4 and CD8 T-cell subsets from peripheral blood by flow cytometry according to their expression of naive and memory markers CD45RA, CD45RO, CD62L, and CCR7. Subsets were defined by a single marker to facilitate future establishment of a clinical-grade procedure for reducing alloreactive T-cell precursors and graft- versus -host disease. T c…
A new model of chronic colitis in SCID mice induced by adoptive transfer of CD62L+ CD4+ T cells: insights into the regulatory role of interleukin-6 o…
2003
<i>Objective:</i> The proinflammatory cytokine interleukin (IL)-6 is involved in various chronic inflammatory processes. IL-6 is a predominant cytokine produced by lamina propria T cells in Crohn’s disease and experimental colitis. This study was designed to examine the effect of a neutralizing IL-6-receptor (IL-6R) antibody on the programmed cell death of mucosal T cells in the CD62L+ CD4+ SCID transfer model of chronic experimental colitis in mice and to gain more insight into the pathogenesis of this transfer colitis model. <i>Methods:</i> For adoptive transfer, we isolated CD62L+ CD4+ double-positive T cells from wild-type BALB/c mice followed by intraperitoneal …
Local blockade of IL-6R signaling induces lung CD4+ T cell apoptosis in a murine model of asthma via regulatory T cells.
2007
We previously reported high levels of the soluble form of the IL-6R (sIL-6R) in the airways of asthmatic subjects. Here, we analyzed the IL-6R effects on Th2 cell survival in the lung by locally antagonizing sIL-6R-mediated trans-signaling with a designer fusion protein (gp130-Fc) as well as IL-6R signaling with an antibody against the gp80 unit of the IL-6R (alphaIL-6R) in a murine model of asthma after ovalbumin peptide (OVA) sensitization and challenge. Blockade of the sIL-6R led to a significant decrease in inflammatory cells by an apoptosis-independent mechanism. In contrast, local treatment with alphaIL-6R antibodies that also block signaling via the membrane-bound IL-6R (mIL-6R) led …