1,721,484 research outputs found
The pathophysiological role of Chemokines in the regulation of NK cell tissue homing
No full textNatural killer (NK) cells are an essential component of innate immunity that can rapidly detect and respond to malignant or infected cells. Chemokines play important roles in directing immune responses by controlling tissue homing, retention, and activation of immune cells. Although some chemokines can promote tumor growth and metastasis, others are responsible for extensive infiltration of lymphocytes, thus resulting in a protective anti-tumor immune response. Here, we summarize discoveries that have revealed the role of specific chemokines in regulating the function of NK cells during inflammation, infection, and malignancies
Vitamin D3: a transcriptional modulator of the interferon-gamma gene.
No full text1 alpha,25-Dihydroxyvitamin D-3 [1(2)25-(OH)(2)D-3] exerts several effects on the immune system, by regulating lymphocyte proliferation, differentiation of monocytes and secretion of cytokines as IL-2, granulocyte-macrophage colony-stimulating factor and IFN-gamma in T cells. Here, we analyze the effect of 1,25-(OH)(2)D-3 on IFN-gamma gene transcription. Transient transfection assays in Jurkat T cells indicate that activation of the IFN-gamma promoter is down-regulated by 1,25-(OH)(2)D-3. This effect is enhanced by retinoid X receptor (RXR), and a functional Vitamin D-3 receptor (VDR) DNA-binding domain in necessary for repression. We delineated two important promoter regions mainly involved in this modulation. The first of these is situated at the level of a promoter-silencer previously characterized and binds the heterodimer VDR-RXR in electrophoretic mobility shift assay. Residual negative regulation was also detected at the level of the promoter fragment -108 to +64 bp from the transcription start site and, surprisingly, the activity of the IFN-gamma enhancer from -108 to -36 bp in the context of a heterologous promoter was not affected by 1,25-(OH)(2)D-3. Moreover, binding activity for VDR-RXR has been detected in the IFN-gamma minimal promoter, suggesting a possible mechanism of interference with transcription initiation/progression. The overall data indicate that direct modulation of the IFN-gamma promoter activity is one of the possible mechanisms involved in the repressive effect of 1,25-(OH)(2)D-3 on IFN-gamma gene expression
Structure and function of the CC chemokine receptor (CCR) 8.
No full textThe CC chemokine receptor (CCR) 8 belongs to the seven transmembrane-spanning receptor family and functionally responds to the eukaryotic CC chemokines I-309, thymus and activation-regulated chemokine, macrophage inflammatory protein-1 beta (MIP-1b) and to the products viral MIP-I and viral MIP-II of the Kaposi-associated herpesvirus (HHV-8). Although it has not yet been fully characterised, its restricted expression to lymphoid tissues, i.e. thymus, spleen and lymph nodes, and its abundant up-regulation in Th2 lymphocytes suggest a potential role in lymphocyte activation, migration and differentiation and in allergic diseases. In this article we review the data known up to now related to CCR8 from cloning to protein structure, expression patterns and functional activation by its agonists
Memory T-cell competition for bone marrow seeding
No full textThe presence in the bone marrow of memory CD8 T cells is well recognized. However, it is still largely unclear how T-cell migration from the lymphoid periphery to the bone marrow is regulated. In the present report, we show that antigen-specific CD4 T cells, as well as antigen-specific CD8 T cells, localize to the bone marrow of immunized mice, and are sustained there over long periods of time. To investigate the rules governing T-cell migration to the bone marrow, we generated chimeric mice in which the lymphoid periphery contained two genetically or phenotypically distinct groups of T cells, one of which was identical to the host. We then examined whether a distinct type of T cell had an advantage over the others in the colonization of bone marrow. Our results show that whereas ICAM1 and CD18 molecules are both involved in homing to lymph nodes, neither is crucial for T-cell bone marrow colonization. We also observed that memory-phenotype CD44(high) T cells, but not virgin-type CD44(-/low) T cells, preferentially home to the bone marrow upon adoptive transfer to normal young mice, but not to thymectomized old recipients where an existing memory T-cell pool precludes their free access. Thus, T-cell colonization of the bone marrow uses distinct molecules from those implicated in lymph node homing, and is regulated both by the properties of the T cell and by the competitive efficacy of other T cells inhabiting the same, saturable niche. This implies that the homing potential of an individual lymphocyte is not merely an intrinsic property of the cell, but rather a property of the lymphoid system taken as a whole
Integrin-mediated stimulation of tyrosine phosphorylation in lymphoid cells.
No full text[No abstract available
Interferon-alpha, beta and tumor necrosis factor-alpha enhance the frequency of miniature end-plate potentials at rat neuromuscular junction.
No full textThe effects of the two cytokines, rat interferon-alpha, and human tumor necrosis factor-alpha, were studied at the rat neuromuscular junction by using classical electrophysiological techniques. Both cytokines in a similar way at concentrations of 2,000 and 35,000 U/ml, respectively, increased transiently and with a relatively long delay (15 to 25 min) the frequency of mimiature endplate potentials. The observed effects may be related to complex second messenger mechanisms and contribute to modulation and plasticity of neurotransmission
Lymphokine-activated tumor inhibition in vivo. I. The local administration of interleukin 2 triggers nonreactive lymphocytes from tumor-bearing mice to inhibit tumor growth
No full textCE-2 is a chemically induced tumor of low immunogenicity in syngeneic BALB/c mice. Nylon wool columns eluting lymphocytes from the spleen of mice bearing clinically evident (5-mm mean diameter) CE-2 tumors (CE-2 TB lymphocytes) do not react with CE-2 cells in vitro, nor are they able to affect their growth in vivo in a Winn-type neutralization assay at 5:1 lymphocyte:tumor cell ratio. However, they become able to inhibit CE-2 tumor growth when 20 U of interleukin 2 (IL 2) in 0.4 ml are injected daily for 10 days at the challenge site. In contrast, mice injected with CE-2 cells and IL 2 only display tumor takes and growth that are not significantly different from those in controls challenged with CE-2 cells alone. This lymphokine-activated tumor inhibition (LATI) is not a peculiarity of the CE-2 tumor-host combination, because different tumors can be inhibited in this way and various TB lymphocytes can initiate it. In these experiments, IL 2-rich 25,000 to 30,000 m.w. fractions were obtained routinely from the culture supernatants of a clone of EL-4 thymoma stimulated with phorbol myristic acetate. Equally active IL 2-rich preparations were obtained from rat spleen cells stimulated with concanavalin A, or from MLA 144 gibbon lymphosarcoma spontaneously releasing IL 2. Treatment of CE-2 TB lymphocytes with various antibody and C, with 2000 rad γ-irradiation, or fractionation on Percoll density gradients suggested that radioresistant functions of Thy-1.2+, Lyt-1.2, Lyt-2.2- and of asialo GM1+ cells are independently involved in LATI induction. These lymphocytes inhibit tumor growth by recruiting the radiosensitive effector mechanisms of the recipient mice required for ultimate tumor destruction. CE-2 tumor inhibition by LATI leaves a specific delayed-type hypersensitivity and an immunologic memory, resulting in rejection of a second lethal CE-2 challenge in a significant number of mice
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