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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the fetus is considered to be an "allograft" there is little information concerning the role of lymphokines in human pregnancy. Lymphokines are polypeptides secreted by stimulated lymphocytes that direct the immune response by enabling immune effector cells to communicate with each other. To characterize lymphokine production during normal human pregnancy, we isolated peripheral leukocytes and decidual lymphocyte-like cells from women undergoing repeat cesarean section at term. After stimulation with mitogen and paternal antigen for 24 hours, culture supernatants were assayed for granulocyte-macrophage colony-stimulating factor and interleukin-2 by enzyme-linked immunosorbent assay. There was no difference in the amount of interleukin-2 produced by stimulated peripheral and decidual cells. However, granulocyte-macrophage colony-stimulating factor production by stimulated decidual lymphocyte-like cells was significantly greater than granulocyte-macrophage colony-stimulating factor produced by peripheral lymphocytes. Decidual lymphocyte-like cells produced granulocyte-macrophage colony-stimulating factor both spontaneously and after stimulation with mitogen or paternal antigen, whereas peripheral leukocytes did not. This suggests that the decidua constitutes a distinct immunologic microenvironment.
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PMID:Lymphokine production during term human pregnancy: differences between peripheral leukocytes and decidual cells. 225

Using lymph node lymphocytes of Leishmania major-infected mice, we constructed and cloned two T-cell hybridomas that could activate macrophages to exert antileishmanial defense in vitro. One clone, 1D5, produced lymphokines (including gamma interferon) that induced these effects. Production of the macrophage-activating lymphokines and the protective effect of 1D5 were suppressed by the addition of cyclosporine A to cultures. The other clone, 1B6, produced no detectable macrophage-activating lymphokines, and its protective ability was not suppressed by cyclosporine A. Granulocyte-macrophage colony-stimulating factor (a lymphokine also known to induce antileishmanial effects in macrophages) was not detectable in culture supernatants of either clone. Furthermore, neither clone was cytotoxic to infected macrophages. Antileishmanial defense induced by 1B6 was genetically restricted; that is, infected macrophages and hybridoma cells had to be syngeneic for an antileishmanial effect to occur. In contrast, such restriction was not a property of clone 1D5, a clone that was responsive to alloantigens as well as leishmanial antigens. When incubated at a temperature (34 degrees C) at which lymphokines are relatively ineffective for antileishmanial defense, 1B6 but not 1D5 retained its antileishmanial properties. These observations provide clear evidence for the existence of two distinct mechanisms of macrophage activation: one that is lymphokine dependent, and one that is apparently lymphokine independent. The expression of these two mechanisms by cloned cells strongly suggests that they are properties of different T-cell subpopulations, extending our prior conclusions based on studies of heterogeneous T-cell populations. We hypothesize that the latter macrophage activation process involves a cell contact-dependent mechanism which might involve the interaction of a lymphocyte membrane-associated macrophage-activating factor (such as tumor necrosis factor) with its receptor on the macrophage, resulting in activation of antileishmanial effects but not host cell cytotoxicity.
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PMID:T-cell hybridomas reveal two distinct mechanisms of antileishmanial defense. 232 12

Lymphokine gene expression was examined in a panel of 116 short-term murine T-lymphocyte clones derived by single-cell micromanipulation from allogeneic mixed leukocyte cultures. About 30% of clonable T cells, including both CD4+ CD8- and CD4- CD8+ cells, could be expanded for assay at an average of 22 days after cloning. By RNA blot-hybridization analysis, most clones (85-96%) expressed detectable granulocyte-macrophage colony-stimulating factor, interleukin 3, and gamma interferon mRNAs, and 11% expressed interleukin 4 mRNA. Although no differences were noted between CD4+ and CD8+ clones in the combinations of lymphokines produced, CD4+ clones on average transcribed and secreted higher levels. When the frequencies of coexpression of any pair of lymphokine mRNAs were determined, all were found to correspond to the values predicted for random assortment of the individual frequencies. For example, among 13 interleukin 4-positive clones, 11 also transcribed gamma interferon, giving the frequency of double-positive clones expected for random association (9.6% versus 10.8%). Therefore, expression of the four lymphokine genes segregated independently among the clones and did not allow the division of T cells into subsets with distinct patterns of lymphokine synthesis.
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PMID:Coexpression of granulocyte-macrophage colony-stimulating factor, gamma interferon, and interleukins 3 and 4 is random in murine alloreactive T-lymphocyte clones. 246 63

CD28 is a 44-kDa glycoprotein expressed as a homodimer on the surface of a major subset of human T cells. Previous studies have demonstrated that the binding of monoclonal antibodies to the CD28 surface antigen can augment the proliferation of purified human T cells stimulated with suboptimal doses of mitogens or anti-T-cell receptor/CD3 complex antibodies. In this report, we show that CD28 stimulation augments T-cell immune responses by specifically inducing a 5- to 50-fold enhancement in the expression and secretion of interleukin 2, tumor necrosis factor type alpha, lymphotoxin, interferon gamma, and granulocyte-macrophage colony-stimulating factor in normal human T cells stimulated to proliferate by crosslinking of the T-cell receptor/CD3 complex. This CD28-mediated induction of lymphokine/cytokine gene expression occurred even in T cells stimulated with optimal concentrations of mitogens or anti-T-cell receptor/CD3 antibodies, although under these conditions CD28 activation failed to enhance the proliferative response. The activation pathway induced by stimulation of CD28 is distinct from other biochemical pathways that induce lymphokines/cytokines because CD28 stimulation can induce lymphokine/cytokine gene expression in the presence of the immunosuppressant cyclosporine. Together these data suggest that the CD28 cell surface molecule is part of a distinct activation pathway that specifically modulates the expression of multiple lymphokine/cytokine genes.
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PMID:CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines. 246 50

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known as an inducer of proliferation and functional activation of myeloid cells. This study was carried out to characterize the effects of GM-CSF on polymorphonuclear leukocytes (PMN) more extensively. Using Northern blot analysis, we show that PMN are able to accumulate mRNAs for different cytokines, including tumor necrosis factor-alpha (TNF-alpha); G-CSF, and M-CSF, all of which are involved in inflammation and hematopoiesis. Biological assays and immunoassays demonstrate that PMN translate these mRNAs, except TNF-alpha, into secretory proteins. However, the expression of these cytokines is dependent on stimulation by exogenous signals, preferentially provided by the T cell-derived lymphokine GM-CSF. Stimulation of hematopoiesis and amplification of defense mechanisms after T cell activation thus might involve not only monocytes but also PMN, a cell type previously believed to be biosynthetically inactive.
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PMID:Granulocyte-macrophage colony-stimulating factor induces cytokine secretion by human polymorphonuclear leukocytes. 1456 12

Two lymphokines that contribute to induction of cell differentiation in promyelocytic HL-60 leukemia cells by human T-cell lymphoma HUT-102 cells were identified previously. The lymphokines identified in the differentiation-inducing preparation were interferon-gamma (IFN-gamma) and lymphotoxin. To determine the remaining component(s) of this differentiation-inducing activity, we used gene-cloned (recombinant) forms and antibodies of lymphokines. The differentiation-inducing activity of the HUT-102 cells was not completely neutralized by the antibodies, suggesting that an additional lymphokine(s) is involved. Granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with retinoic acid induced differentiation of the HL-60 cells in a dose-dependent manner. Furthermore, the activity of the differentiation-inducing factors was partially inhibited by anti-GM-CSF antibody and completely inhibited by the combination of antibodies to lymphotoxin, IFN-gamma, and GM-CSF. These results indicate that, in addition to IFN-gamma and lymphotoxin, GM-CSF is the third major component released by HUT-102 cells for inducing differentiation of HL-60 cells.
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PMID:Identification of components of differentiation-inducing activity of human T-cell lymphoma cells by induction of differentiation in human myeloid leukemia cells. 249 90

The susceptibilities of human blood monocytes and alveolar macrophages (AM) to cytotoxicity mediated by lymphokine (IL-2)-activated killer (LAK) cells were examined. Monocytes and AM of healthy donors were obtained by counter-flow centrifugal elutriation (CCE) and bronchoalveolar lavage, respectively. The LAK activity induced by incubation of blood mononuclear cells (MNC) for 4 days with recombinant interleukin 2 (IL-2) was measured by a 4-h 51Cr release assay. The LAK cells were not cytotoxic to freshly isolated monocytes, but were cytotoxic to autologous fresh AM and monocytes that had been incubated for more than 4 days in medium alone. Blood monocytes that had been incubated for 4 days in medium with granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF) or interleukin 3(IL-3) were much more susceptible than untreated monocytes to the cytotoxicity of LAK cells. When blood monocytes were separated by CCE into subpopulations of three sizes (small, medium and large), the medium- and large-sized monocytes showed greater responses to GM-CSF in terms of DNA synthesis and colony formation than the small-sized cells. After treatment with GM-CSF for 4 days, these medium and large monocytes were more susceptible than the small monocytes to the cytotoxic action of LAK cells. These results suggest that LAK cells may be important in situ in down-regulating the functions of mature macrophages and blood monocytes that have responded to GM-CSF.
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PMID:Killing of alveolar macrophages and of monocytes that have responded to granulocyte-macrophage colony-stimulating factor by human lymphokine-activated killer cells. 250 89

Granulocyte-macrophage colony-stimulating factor (GmCSF) is a lymphokine secreted by class II major histocompatibility complex (MHC)-restricted T cells after lectin or antigen stimulation. To investigate the relationship between interleukin-2 (IL-2) and GmCSF production, we utilized long-term cultures of porcine myelin basic protein (PMBP)-specific T helper cell clones that were maintained with IL-2 in the absence of antigen or irradiated antigen-presenting cells (APC). We have found that supernatants of these T cell clones contained GmCSF activity after IL-2 stimulation. Inhibition of cell proliferation by irradiation failed to stop GmCSF production. When these clones were stimulated with PMBP and irradiated APC in the presence of anti-IL-2 receptor antibody, the T cell supernatants still contained GmCSF activity. These results indicate that (1) GmCSF production by T helper clones after IL-2 stimulation is independent of cell proliferation and (2) antigen/MHC-stimulated GmCSF production by T cell clones can occur by an IL-2-independent pathway.
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PMID:Murine T helper cell clones secrete granulocyte-macrophage colony-stimulating factor (GmCSF) by both interleukin-2-dependent and interleukin-2-independent pathways. 252 42

Protective immunity to lethal Candida albicans challenge in vivo and activation of splenic macrophages with highly candidacidal activity in vitro were detected in mice infected with low-virulence agerminative yeast cells of the variant strain PCA-2, at a time when a strong delayed-type hypersensitivity (DTH) reaction to C. albicans occurred in the footpads of PCA-2-treated mice. The DTH reaction was transferable with spleen cell populations from these animals, and enrichment of splenic lymphocytes in L3T4+ cells significantly increased the footpad swelling. The reactivity transferred by L3T4+ cells was a radiosensitive (2,500 rads in vitro) phenomenon that required collaboration with radioresistant, silica-sensitive syngeneic cells in the host and was inhibited by treatment of recipient mice with antibodies to the L3T4 antigen or murine gamma interferon. In vitro, the PCA-2-immune L3T4+ cells produced various lymphokine activities upon incubation with C. albicans, including gamma interferon and granulocyte-macrophage colony-stimulating factor. Anti-L3T4 monoclonal antibody treatment of PCA-2-infected mice significantly impaired their footpad reaction and resistance to C. albicans, as shown by increased recovery of yeast cells from the kidneys of anti-L3T4-treated mice. These results suggested that the mechanisms of anti-Candida resistance induced by PCA-2 may involve specific induction of a DTH response mediated by inflammatory L3T4+ T cells and lymphokine-activated phagocytic effectors. However, the survival rate of the PCA-2-immune mice challenged with C. albicans was not significantly modified by administration of the anti-L3T4 antibody, thus allowing for the conclusion that compensatory mechanisms lead to considerable anti-Candida resistance when the activity of L3T4+ cells is deficient.
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PMID:Role of L3T4+ lymphocytes in protective immunity to systemic Candida albicans infection in mice. 257 56

Cultured human monocytes have been shown to be susceptible to lysis by autologous lymphokine-activated killer (LAK) cells. To determine factors that might modulate the sensitivity of monocytes to lysis, we cultured adherent peripheral blood leukocytes (PBL) in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) since these cytokines have been reported to affect both functional and physical characteristics of monocytes. Both recombinant human GM-CSF and IL-3 were found to significantly enhance the susceptibility of monocytes to lysis by LAK cells in a dose-dependent manner, with GM-CSF being slightly more effective. In a kinetics study, the lysability of monocytes increased after two days of incubation with either cytokine, with maximal susceptibility occurring after four to six days of culture. The effects of GM-CSF and IL-3 appeared to be specific for monocytes since culture of either nonadherent cells or granulocytes, which are normally resistant to LAK-mediated lysis, did not induce sensitivity. While the effects of GM-CSF and IL-3 have been shown to be synergistic in some cases, they did not act synergistically to induce monocyte susceptibility to LAK lysis. In cold target experiments cytokine-treated monocytes reciprocally blocked lysis, suggesting that similar target structures were modulated with either factor. FACS analysis and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated comparable modulation of surface antigens with either GM-CSF or IL-3. Thus, these cytokines can serve to augment susceptibility of monocytes to LAK cells, emphasizing the complex interactions that occur in the immune system.
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PMID:Susceptibility of monocytes to lymphokine-activated killer cell lysis: effect of granulocyte-macrophage colony-stimulating factor and interleukin-3. 264 72


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