UNIPROT:P04141 - FACTA Search

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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)

Attempts have been made to isolate continuous lines of rare subsets of lymphoid cells present in murine spleen in order to analyse their function and lineage relationship with respect to other lymphoid cells. Mitogenic stimulation was used to expand the lymphoid cells remaining in spleen following depletion of CD4+ and CD8+ T cells by antibody and complement treatment. Cells were cultured in the presence of concanavalin A (Con A), interleukin-2 (IL-2) and syngeneic irradiated spleen feeder cells. This procedure expanded a population of non-T-, non-B-lymphoid cells bearing a common, unique phenotype resembling lymphoid precursors. Eight cloned lines from B10.A(2R) and B10.A(5R) strains of mice have been analysed here. Analysis of cell surface marker expression has revealed positive expression of class I and class II major histocompatibility complex (MHC) antigens, CD44, CD45 (T200 and B220) but expressing no markers unique to T, B or myeloid cells. All cell lines represent agranular lymphoblasts and show no evidence of early T-cell receptor (TcR) or Ig heavy chain gene rearrangements, suggesting no commitment to T-or B-lymphoid lineage. Despite expression of the NK1.1 marker for natural killer (NK) cells, none of the cell lines has been shown to have cytotoxic function for NK targets, nor could cytotoxic function be induced following various activation procedures. Analysis of lymphokine production has revealed no detectable IL-1, IL-2, IL-3, IL-4, IL-5, tumour necrosis factor-alpha (TNF-alpha) or granulocyte-macrophage colony-stimulating factor (GM-CSF) in cell supernatants. However, all but one of these cell lines constitutively produce IL-6. Each cell line has been shown to induce T-cell proliferation independently in mixed lymphocyte reactions, implicating the capacity of these cells to act as antigen-presenting cells. Consistent with this hypothesis is the observation that these cells also demonstrate endocytic activity for foreign proteins. This was visualized by their uptake of fluoresceinated albumin into cytoplasmic granules. Since they express many cell surface markers common to described isolates of spleen dendritic cells, including both class I and class II major histocompatibility molecules, they would appear to represent the first example of continuous lines of this rare cell subset.
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PMID:Characterization of unique lymphoid cells derived from murine spleen which constitutively produce interleukin-6. 834 1

Tumor infiltrating lymphocytes (TIL) were cultured from 17 B-cell lymphoma specimens derived from patients with predominantly low-grade malignancies. Specimens included 15 lymph-node biopsies, 1 malignant pleural effusion, and PBL from 1 patient with circulating lymphoma cells. The phenotypic and proliferative characteristics of TIL cultured in interleukin-2 (IL-2) were studied, as well as cytolysis and cytokine secretion in response to autologous tumor. Flow cytometry of fresh tumor suspensions showed that 50% of cells (median) were malignant B cells and 36% were infiltrating T lymphocytes. After culture for approximately 1 month, TIL were 75% +/- 8% CD3+ (mean +/- SEM), 47% +/- 8% CD4+ and 35% +/- 7% CD8+. TIL proliferation was modest in most cases: the median maximum expansion was 32-fold in 25 days. Lysis of autologous tumor in 4-hour 51Cr release assays was mediated by 2 of 12 TIL studied, but was nonspecific. However, these same two TIL, when cocultured with various tumor stimulators, preferentially secreted tumor necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor after autologous tumor stimulation; unstimulated TIL secreted undetectable or barely detectable levels of these cytokines. In one TIL culture, cytokines were secreted by purified CD4+ TIL but not by CD8+ cells, and secretion was completely abrogated by the anti-major histocompatibility complex (MHC) class II antibody IVA12. Thus, although specific cytokine secretion by lymphoma TIL in response to autologous tumor was observed, it occurred in fewer than 20% of patients studied.
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PMID:Tumor-infiltrating lymphocytes derived from select B-cell lymphomas secrete granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha in response to autologous tumor stimulation. 835 84

The mycoplasmas are a diverse set of bacteria that, in the course of their interactions with cells of the immune system, have a wide range of immunomodulatory effects. These effects include polyclonal stimulation of proliferation of T and B lymphocytes; activation of cytolytic activity of macrophages, natural killer cells, and cytotoxic T cells; and stimulation of production of cytokines (interleukin [IL]-1, IL-2, IL-4, IL-6, interferon [IFN]-alpha, IFN-beta, IFN-gamma, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor [GM-CSF]) by immunocompetent cells. Mycoplasmas have also been shown to induce major histocompatibility complex (MHC) expression in macrophage cell lines and cultures. This report demonstrates that induction of MHC expression by mycoplasmas is directly due to increases in the transcriptional activity of MHC genes. Experiments attempting to determine if the mechanism responsible for these increases in MHC expression requires the production of cytokines have demonstrated that production of IFN-gamma, IL-4, and GM-CSF is probably not involved.
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PMID:Mycoplasmal induction of cytokine production and major histocompatibility complex expression. 839 13

Activation of a primary T-lymphocyte response requires additional signals apart from interaction of the T-cell receptor (TcR)/CD3 complex with major histocompatibility complex (MHC) antigens on the antigen-presenting cell. The CD28 antigen on T lymphocytes provides an important co-stimulatory signal to T lymphocytes and we therefore searched for the presence of its ligand, the B7/BB-1 antigen, on blood and tonsil dendritic cells (DC). Blood DC, prepared from peripheral blood mononuclear cells with a minimal period of in vitro culture, did not stain with the monoclonal antibody BB-1 using flow cytometry analysis. In contrast, tonsil DC stained weakly for B7/BB-1 compared to positive control cell lines. Polymerase chain reaction (PCR) was used to amplify a 605 base pair (bp) fragment from human B7/BB-1 mRNA and demonstrated significant amounts of B7/BB-1 mRNA in tonsil DC but no specific product was obtained from blood DC, confirming the surface-staining results. Weak expression of B7/BB-1 antigen was detected by immunofluorescence analysis following culture of blood DC with either interferon-gamma (IFN-gamma) or granulocyte-macrophage colony-stimulating factor (GM-CSF). These data support the concept that blood DC give rise to tissue and/or lymphoid DC, which acquire co-stimulatory ligands as a result of activation and/or differentiation.
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PMID:B7/BB-1 is a leucocyte differentiation antigen on human dendritic cells induced by activation. 840 86

The developmental origin of dendritic cells, a specialized system of major histocompatibility complex (MHC) class II-rich antigen-presenting cells for T-cell immunity and tolerance, is not well characterized. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to stimulate dendritic cells, including growth and development from MHC class II-negative precursors in suspension cultures of mouse bone marrow. Here we studied colony formation in semi-solid methylcellulose cultures, a classical bioassay system in which GM-CSF induces the formation of mixed granulocyte-macrophage colonies. When colonies were induced from MHC class II-negative precursors, a small subset (1-2%) of typical dendritic cells developed alongside macrophages and granulocytes. The dendritic cells were distinguished by their cytologic features, high levels of MHC class II products, and distinct intracellular granule antigens. By using differential adherence to plastic, enriched populations of the various myeloid cell types were isolated from colonies. Only the dendritic cells stimulated a primary T-cell immune response, the mixed leukocyte reaction, and the potency was comparable to typical dendritic cells isolated from spleen. Macrophages from mixed or pure colonies were inactive as stimulator cells. Therefore, three distinct pathways of myeloid development--granulocytes, macrophages, and dendritic cells--can develop from a common MHC class II-negative progenitor under the aegis of GM-CSF.
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PMID:Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class II-negative progenitor in mouse bone marrow. 846 20

The heterogeneity of the thymic stroma has made careful characterization of particular thymic stromal cell types difficult. To this end, we have derived a panel of cloned thymic stromal cell lines from simian virus 40 T antigen (SV40-T antigen) transgenic mice. Based on their analysis with monoclonal antibodies that distinguish among subsets of thymic stroma cells, and on the morphology and ultrastructural features of the different clones, we suggest that our panel includes representatives of the thymic subcapsular cortex or thymic nurse cells (427.1), the deep cortex or cortical reticular cells (1308.1) and the medulla including medullary interdigitating (IDC)-like cells (6.1.1) and medullary epithelial cells (6.1.7). A fifth cell type of undesignated but apparent medullary origin (6.1.11) was also isolated. All of the cell lines constitutively express the SV40 T antigen transgene and the class I antigens of the major histocompatibility complex (MHC), and they can be induced to express MHC class II antigens upon stimulation with recombinant interferon-gamma (IFN-gamma). These cell lines elaborate a factor(s) that induces the proliferation of cells from the fetal liver and bone marrow, but not from the neonatal thymus. A factor(s) elaborated by the 1308.1 cell line also induces the proliferation of fetal thymocytes in the absence of mitogens, phorbol esters or calcium ionophore which is augmented with the addition of recombinant interleukin-2 (IL-2). Analysis by reverse transcription polymerase chain reaction with primers for some mouse cytokines reveals that each of these cell lines contain granulocyte-macrophage colony-stimulating factor (GM-CSF) transcripts and that 1308.1, 6.1.1 and 6.1.7 produce IL-6 mRNA. Cell lines 1308.1 and 6.1.1 also produce IL-7; 6.1.1 produces IL-1 beta and tumor necrosis factor (TNF)-alpha while the 427.1 cell line produces IL-5 and IFN-gamma mRNA. None of the cell lines tested express the IL-2 receptor, IL-2, IL-3, IL-4, TNF-beta or macrophage inflammatory proteins mRNA. Conditioned medium (CM) from 1308.1 and 6.1.11 induced differentiation of cells purified from the mouse fetal liver into granulocytes; 1308.1 CM also induced differentiation of the mouse hematopoietic stem cell line 32DCl3(G) suggesting that the CM contains granulocyte (G)-CSF activity. Each cell line produces GM-CSF but the greatest activity is associated with 1308.1 and 6.1.11 CM. The availability of these well-characterized, functional, cloned thymic stromal cells will allow a more detailed analysis of the role of each cell type in both myeloid and T cell development.
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PMID:Phenotypically diverse mouse thymic stromal cell lines which induce proliferation and differentiation of hematopoietic cells. 850 May 19

Multilineage donor-derived hematopoietic cell chimerism is a persistent feature of spontaneously tolerant mouse liver allograft recipients. We have shown previously that normal liver-derived precursors of "chimeric" dendritic cells (DC) propagated in vitro migrate in vivo to T-dependent areas of allogeneic lymphoid tissue, where they or their progeny appear to persist indefinitely. In this study, granulocyte-macrophage colony-stimulating factor (GM-CSF)+interleukin-4 (IL-4) were used to propagate DC progenitors from freshly isolated mouse bone marrow. The progenitor cells gave rise in 7-10 days to potent antigen-presenting cells (APC) that stimulated naive allogeneic T cells in primary mixed leukocyte cultures (MLC). The culture method, together with the reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of donor and recipient strain major histocompatibility complex (MHC) class II mRNA was used to test whether donor-derived DC could be propagated from the bone marrow of unmodified, orthotopic liver allograft recipients. Freshly isolated bone marrow from these transplanted animals contained small numbers of donor cells and responded to GM-CSF+IL-4 stimulation. In addition to cells expressing recipient (B10) phenotype (H-2Kb+; Iab+), a minor population of donor (B10.BR)-derived cells (H-2Kk+; Iak) were also propagated from liver graft recipients euthanized two weeks posttransplant. DC sorted from these cultures exhibited stimulatory activity for recipient strain T cells consistent with a low level (< 1%) of donor DC propagation. The immunologic role of donor-derived DC progenitors in liver allograft recipients and its relation to the induction and maintenance of donor-specific unresponsiveness remains to be determined.
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PMID:Identification of donor-derived dendritic cell progenitors in bone marrow of spontaneously tolerant liver allograft recipients. 854 89

We studied major histocompatibility complex (MHC) and cytokine mRNA induction after renal injury in the absence of interferon-gamma (IFN-gamma) using IFN-gamma gene knockout (GKO) mice. The left renal pedicle of normal (wild-type) and GKO BALB/c mice was clamped for 60 minutes; cytokine and MHC mRNA expression were monitored in the injured kidney and compared to the contralateral control kidney. After a single episode of ischemic injury, the expression of mRNA for MHC class I and II, interleukin-2, interleukin-10, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and transforming growth factor-beta 1 was increased in wild-type and GKO mice, whereas preproepidermal growth factor (ppEGF) was reduced. IFN-gamma expression was induced in wild-type mice but absent in the GKO mice. Therefore, local injury was equally effective in both wild-type and GKO mice with equivalent cytokine and MHC mRNA induction, proving that local tissue injury can induce MHC expression by non-IFN-gamma factors.
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PMID:Acute renal injury in the interferon-gamma gene knockout mouse: effect on cytokine gene expression. 854 90

Human Langerhans cells (LC) are CD1a+ dendritic cells (DC) that function as potent antigen-presenting cells for primary and secondary immune responses. Limitations in DC/LC numbers, imposed by difficult and tedious isolation procedures, have so far precluded their use as immunogens in the generation and/or augmentation of host responses against various pathogens. Therefore, we have developed a procedure for the generation of human DC/LC from CD34+ hematopoietic progenitor cells (HPC) isolated (mean: 0.7 x 10(6)/ buffy coat and 2.6 x 10(6)/leukapheresis product) and purified ( > 95%) from the peripheral blood of healthy adults. In vitro stimulation of these cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF)-alpha led to their vigorous proliferation and differentiation resulting in the emergence of CD45+/CD68+/CD3-/CD19-/CD56- leukocytes some of which (mean: 12%) express CD1a and exhibit anti-CD4 and anti-major histocompatibility complex (MHC) class II reactivity. These CD1a- leukocytes include (1) LC as evidenced by the presence of Birbeck granules (BG), (2) CD14+ monocytes, and (3) Birbeck granule-negative cells with a dendritic morphology. Addition of interleukin (IL)-4 to the cytokine cocktail interfered with the development of monocytes and led to a reduction in the overall yield but, on the other hand, resulted in an increased percentage of CD1a+ cells (mean: 24%) among all cells generated. In vitro generated CD1a+, but not CD1a- HPC-derived cells are potent stimulators of the primary mixed leukocyte reaction and, as such, promising candidates for vaccination purposes.
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PMID:Generation of human dendritic cells/Langerhans cells from circulating CD34+ hematopoietic progenitor cells. 860 17

We have previously shown that tumor necrosis factor (TNF)alpha strongly potentiates the granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin (IL)-3-dependent proliferation of CD34+ hematopoietic progenitor cells (HPC) through the recruitment of early progenitors with high proliferative potential. Furthermore, the combination of GM-CSF and TNFalpha allows the generation of large numbers of dendritic/Langerhans cells (D-Lc). Herein, we analyzed whether IL-3, when combined to TNFalpha would, as does GM-CSF, allow the generation of CD1a+ D-Lc. Accordingly, cultures of cord blood CD34+ HPC with IL-3 + TNFalpha yielded 20% to 60% CD14+ cells and 11% to 17% CD1a+ cells, while IL-3 alone did not generate significant numbers of CD1a+ cells. Although the percentage of CD1a+ cells detected in IL3 + TNFalpha was lower than that observed in GM-CSF + TNFalpha (42% to 78%), the strong growth induced by IL-3 + TNFalpha generated as many CD1a+ cells as did GM-CSF + TNFalpha. The CD14+ and CD1a+ cells generated with IL-3 + TNFalpha are similar to CD14+ and CD1a+ cells generated in GM-CSF alone and GM-CSF + TNFalpha, respectively. CD1a+ cells differed from CD14+ cells by (1) dendritic morphology, (2) higher expression of CD1a, CD1c, CD4, CD40, adhesion molecules (CD11c, CD54, CD58), major histocompatibility complex (MHC) class II molecules and CD28 ligands (CD80 and CD86), (3) lack of Fc receptor FcgammaRI (CD64) and complement receptor CR1 (CD35) expression, and (4) stronger induction of allogeneic T-cell proliferation. Thus, in combination with TNFalpha, IL-3 is as potent as GM-CSF for the generation of CD1a+ D-Lc from cord blood CD34+ HPC. The dendritic cell inducing ability of IL-3 may explain why mice with inactivated GM-CSF gene display dendritic cells.
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PMID:Interleukin-3 cooperates with tumor necrosis factor alpha for the development of human dendritic/Langerhans cells from cord blood CD34+ hematopoietic progenitor cells. 863 Apr 1

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