Search results for "CD4+"
showing 10 items of 566 documents
Multifunctional CD4(+) T cells correlate with active Mycobacterium tuberculosis infection.
2010
Th1 CD4(+) T cells and their derived cytokines are crucial for protection against Mycobacterium tuberculosis. Using multiparametic flow cytometry, we have evaluated the distribution of seven distinct functional states (IFN-gamma/IL-2/TNF-alpha triple expressors, IFN-gamma/IL-2, IFN-gamma/TNF-alpha or TNF-alpha/IL-2 double expressors or IFN-gamma, IL-2 or TNF-alpha single expressors) of CD4(+) T cells in individuals with latent M. tuberculosis infection (LTBI) and active tuberculosis (TB). We found that triple expressors, while detectable in 85-90%TB patients, were only present in 10-15% of LTBI subjects. On the contrary, LTBI subjects had significantly higher (12- to 15-fold) proportions of…
Cyclic adenosine monophosphate is a key component of regulatory T cell–mediated suppression
2007
Naturally occurring regulatory T cells (T reg cells) are a thymus-derived subset of T cells, which are crucial for the maintenance of peripheral tolerance by controlling potentially autoreactive T cells. However, the underlying molecular mechanisms of this strictly cell contact–dependent process are still elusive. Here we show that naturally occurring T reg cells harbor high levels of cyclic adenosine monophosphate (cAMP). This second messenger is known to be a potent inhibitor of proliferation and interleukin 2 synthesis in T cells. Upon coactivation with naturally occurring T reg cells the cAMP content of responder T cells is also strongly increased. Furthermore, we demonstrate that natur…
Tc9 cells, a new subset of CD8+T cells, support Th2-mediated airway inflammation
2013
Similar to T-helper (Th) cells, CD8(+) T cells also differentiate into distinct subpopulations. However, the existence of IL-9-producing CD8(+) T (Tc9) cells has not been elucidated so far. We show that murine CD8(+) T cells activated in the presence of IL-4 plus TGF-β develop into transient IL-9 producers characterized by specific IFN-γ and IL-10 expression patterns as well as by low cytotoxic function along with diminished expression of the CTL-associated transcription factors T-bet and Eomesodermin. Similarly to the CD4(+) counterpart, Tc9 cells required for their differentiation STAT6 and IRF4. Tc9 cells deficient for these master regulators displayed increased levels of Foxp3 that in t…
Functionally Active T Cell Receptor/CD3 Complexes Are Present at the Surface of Cloned Cytotoxic T Cells without Fluorescence-Immunological Detectabi…
1996
The cytotoxic T cell clone 10BK.1 is activated in response to the ovalbumin peptide OVA257-264 in a major histocompatibility complex class I-restricted manner. Following activation 10BK.1 cells proliferate, secrete lymphokines, and kill syn- and allogeneic target cells. Using immunofluorescence analysis we detected CD8, LFA-1, and ICAM-1 on the surface of 10BK.1 cells, but no CD3 or T cell receptor (TCR). In contrast, the proliferative response of 10BK.1 cells to antigen was efficiently blocked by soluble antibodies directed at CD3 epsilon or TCR alpha beta, but not by antibodies directed at TCR gamma delta. In addition, lysis of target cells was blocked by F(ab')2 fragments of antibodies d…
Étude de la régulation transcriptionnelle des lymphocytes Th9
2017
CD4 helper T cells support a wide range of functions due to their ability to differentiate into different effector subsets depending on the antigen encountered and the cytokine environment in which they are. Current knowledge on the differentiation of helper T cells highlights the existence of complex transcriptional networks specific to each T helper subset. In 2008, IL-9 secreting CD4 T cells (Th9) are identified as a new helper T cell subtype. Differentiated in the presence of IL-4 and TGF-β, Th9 cells secrete IL-9 and IL-21, and contribute to the development of autoimmune and allergic diseases. Th9 lymphocytes also exhibit strong anti-tumor properties.The transcriptional network of the …
Distinct Roles for IL-1 Receptor Type I Signaling in Early Versus Established Leishmania major Infections
2006
IL-1alpha/beta released by infected dendritic cells (DC) plays a critical role in the development of protective immunity against Leishmania major. Previous studies demonstrated that treatment of susceptible BALB/c mice with IL-1alpha during T-cell priming (days 1-3 post-infection) induced T helper (Th)1-mediated protection. In contrast, we now demonstrate that prolonged treatment with IL-1alpha (for 3 weeks) worsened disease outcome. To characterize the receptor involved, L. major infections in IL-1 receptor type I (IL-1RI) knockout mice were studied. In C57BL/6 IL-1RI-/- mice, the IL-1alpha-mediated protective effect was abrogated. The course of high-dose infection (2 x 10(5) parasites) in…
Serum leptin and interleukin-6 levels in pediatric patients with HIV.
2003
Recent therapeutic approaches have improved the prognosis of children with HIV. Many new efforts could be involved in their quality of life and therefore could need additional diagnostic strategies. Leptin regulates pubertal development; furthermore a continuous immune stimulus, as in chronic infectious diseases, can enhance leptin's secretion by the action of cytokines such as interleukin (IL)-6. To clarify this role in patients infected with HIV, we assayed leptin and IL-6 and evaluated the influence of HIV severity on its secretion. IL-6 (380.5 +/- 257.6 pg/ml; range: 22-900 pg/ml) showed a significant correlation with leptinemia, HIV-1 RNA, and viremia related to the stage of HIV diseas…
Genome wide identification of new genes and pathways in patients with both autoimmune thyroiditis and type 1 diabetes
2015
Autoimmune thyroid diseases (AITD) and Type 1 diabetes (T1D) frequently occur in the same individual pointing to a strong shared genetic susceptibility. Indeed, the co-occurrence of T1D and AITD in the same individual is classified as a variant of the autoimmune polyglandular syndrome type 3 (designated APS3v). Our aim was to identify new genes and mechanisms causing the co-occurrence of T1D + AITD (APS3v) in the same individual using a genome-wide approach. For our discovery set we analyzed 346 Caucasian APS3v patients and 727 gender and ethnicity matched healthy controls. Genotyping was performed using the Illumina Human660W-Quad.v1. The replication set included 185 APS3v patients and 340…
Role of the protein phosphatase CD45 and lipid rafts in the maintenance of acute myeloblastic leukemiaand development of a new therapeutic treatment
2017
CD45 is a pan-leukocyte protein with tyrosine phosphatase activity involved in the regulation of cytokinereceptors in hematopoiesis, such as the GM-CSF. We report here on new chemical compound,Pyrido[4,3-b]quinoxaline (PyQ), which is a plasma membrane disrupting agent, as a potential drug fortreatment of acute myeloid leukemia (AML). Indeed, we show that the hematopoietic cell lines aremore sensitive to PyQ, compared with non- hematopoietic cell lines. Using HOXA9-MEIS1-transformed blasts from a mouse model to study AML and human primary AML samples, wediscovered that CD45, which is mainly found within plasma-membrane lipid rafts, is rapidly delocalizedafter treatment with PyQ compound. The…
The RNA binding protein tristetraprolin influences the activation state of murine dendritic cells
2010
Abstract Dendritic cells (DCs) serve to maintain peripheral tolerance under steady state conditions. Upon triggering by activation signals they initiate strong immune responses. The activation of DCs is accompanied by a rapid upregulation of proinflammatory cytokines, which were shown in other cell types to be regulated by mechanisms at the transcriptional and posttranscriptional level. Tristetraprolin (TTP), an important RNA binding protein, is involved in the regulation of mRNA stability of such cytokines. In this study we analyzed the significance of TTP for mouse DCs, which were derived from TTP −/− and WT bone marrow progenitor cells (BM-DCs). Unstimulated BM-DCs of TTP −/− mice expres…