Search results for "interleukin-4."
showing 10 items of 119 documents
Potential involvement of IL-9 and Th9 cells in the pathogenesis of rheumatoid arthritis
2015
Objective IL-9 has been shown to be upregulated before the clinical onset of articular disease in RA. The exact role of IL-9 and Th9 cells in RA, however, has not yet been adequately studied. The aim of this study was to evaluate the expression of IL-9 and IL-9-expressing cells in RA patients. Methods IL-9, IL-9R, PU.1, IL-9, thymic stromal lymphopoietin (TSLP), IL-4 and TGF-β expression was assessed by real-time-PCR in the synovial tissues of RA and OA patients. IL-9, IL-9R, IL-4, TSLP and TGF-β were also investigated by immunohistochemistry. Peripheral CD4(+) T cell subsets were studied by flow cytometry analysis before and after incubation with citrullinated peptides. Results IL-9 was ov…
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…
WHOLE BODY IRRADIATION INDUCES IFN-γ PRODUCTION IN BALB/c MICE BY PREVENTING THE APPEARANCE OF A Vα14+NK T DOWNREGULATORY POPULATION
2000
Lymph node cells from TNCB-immune BALB/c mice fail to produce IFN-gamma when exposed to antigen in vitro. Conversely, lymph node cells of irradiated (550 rads) BALB/c mice produce IFN-gamma. Transfer experiments show that normal BALB/c mice contain cells which suppress IFN-gamma production. These downregulatory cells are CD4(+)alpha beta(+)and rearrange the invariant V alpha 14-J alpha 281 T cell receptor alpha chain, thus belonging to the NK T cell subset. Downregulatory cells probably act by producing IL-4 as their effect is blocked by mAb to IL-4.
Methotrexate specifically modulates cytokine production by T cells and macrophages in murine collagen-induced arthritis (CIA): a mechanism for methot…
1999
SUMMARYImmunosuppressive therapy with methotrexate (MTX) has been established as effective treatment for patients with rheumatoid arthritis. To analyse the therapeutic potential and mechanisms of action of MTX, we determined serum cytokine levels and cytokine production by splenic T cells and macrophages in untreated and MTX-treated mice. Furthermore, we assessed the role of MTX in a murine model of experimental arthritis induced by collagen type II (CIA). MTX reduced spontaneous and IL-15-induced tumour necrosis factor (TNF) production by splenic T cells but not by macrophages from healthy mice in vitro in a dose-dependent manner. In contrast, interferon-gamma (IFN-γ) production was less s…
Tcgfiii/p40 is produced by naive murine cd4+ t cells but is not a general t cell growth factor*
1989
Several antigen-specific T cell lines were found to secrete a lymphokine upon activation by antigen or lectin that was provisionally termed T cell growth factor III (TCGF III) because it induced the proliferation of a CD4+ T cell clone independently from IL2 and IL4. Amino acid sequence analysis (and the functional properties of TCGF III) revealed that TCGF III was identical with a recently identified lymphokine termed P40. TCGF III/P40 was not only produced by long-term cultured T cell lines but also upon stimulation of freshly isolated Mlsa-reactive T cells. In addition, naive CD4+ T cells secreted TCGF III/P40 upon activation by lectin or allo-major histocompatibility complex structures.…
Change of Th0 to Th1 cell-cytokine profile following tuberculosis chemotherapy.
2000
T cells mediate protection against tuberculosis, but little is known about their role during chemotherapy of patients with active disease. Here we examined the cytokine profile of CD4 T cells before and after four months of chemotherapy in six initial skin test anergic cases. Purified protein derivative (PPD) and 16-kDa antigen-reactive CD4 T-cell clones prior to therapy resided mostly in disease-associated body fluids and were of the Th0 (interferon (IFN)-gamma + interleukin (IL)-4) secreting profile. In contrast, the majority of postchemotherapy CD4 T-cell clones originated from blood and were of the IFN-gamma secreting Th1 type. However, the recognition of several peptides derived from t…
IL-28A Is a Key Regulator of T-Cell–Mediated Liver Injury via the T-Box Transcription Factor T-Bet
2006
Background & Aims: T-cell–mediated fulminant hepatitis is a potentially life-threatening event for which the underlying pathogenic mechanisms are not fully understood. Here, we demonstrate a key regulatory role of IL-28A in T-cell–mediated hepatitis. Methods: We cloned the murine IL-28A gene by reverse-transcription polymerase chain reaction, assessed the effects of recombinant IL-28A, and generated IL-28A–transgenic mice. Results: IL-28A induced TH1 cytokine production by CD4+ T lymphocytes in a T-bet–dependent manner and was up-regulated in a murine model of T-cell–mediated hepatitis upon Con A administration. In vivo, CD4+ T cells from newly created IL-28A–transgenic animals revealed an …
H2-M, a facilitator of MHC class II peptide loading, and its negative modulator H2-O are differentially expressed in response to proinflammatory cyto…
2000
H2-M is a major histocompatibility complex (MHC) class II-like molecule that catalyzes peptide binding to MHC class II molecules. Recently, the H2-O heterodimer, encoded by H2-Oa and H2-Ob in the MHC class II region, has been shown to be physically associated with H2-M in B cells and to downregulate H2-M function. Examination of H2-O expression in freshly isolated mouse organs revealed that H2-Oa- and H2-Ob-specific transcripts are present in both lymphoid and nonlymphoid tissues. To evaluate the gene regulation and functional impact of H2-O on antigen presentation, we examined the effects on MHCII, invariant chain (Ii), H2-M, and H2-O gene expression of interleukin (IL)-4, IL-10, and inter…
Thyroid Cancer Resistance to Chemotherapeutic Drugs via Autocrine Production of Interleukin-4 and Interleukin-10
2003
We investigated the mechanisms responsible for the widespread refractoriness to chemotherapeutic drugs observed in thyroid cancers. We show that malignant epithelial cells from papillary, follicular, and anaplastic thyroid carcinomas express high levels of Bcl-2 and Bcl-xL. Exogenous expression of either Bcl-2 or Bcl-xL in normal thyrocytes was sufficient to prevent chemotherapeutic drug-induced cytotoxicity. All of the histological thyroid cancer variants examined produced interleukin-4 (IL-4) and interleukin-10 (IL-10), which increased Bcl-2 and Bcl-xL levels and protected thyroid cells from chemotherapeutic agents. Exposure to neutralizing antibodies against IL-4 and IL-10 resulted in do…
Crucial Role of Interleukin-4 in the Survival of Colon Cancer Stem Cells
2008
Abstract Colon tumors may be maintained by a rare fraction of cancer stem-like cells (CSC) that express the cell surface marker CD133. Self-renewing CSCs exhibit relatively greater resistance to clinical cytotoxic therapies and recent work suggests that this resistance may be mediated in part by an autocrine response to the immune cytokine interleukin 4 (IL-4). Blocking IL-4 signaling can sensitize CSCs to apoptotic stimuli and increase the in vivo efficacy of cytotoxic therapy. These findings suggest that inhibitors of IL-4 signaling may offer a new therapeutic tool in colon carcinoma. [Cancer Res 2008;68(11):4022–5]