Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06126 (CD1a)
 2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To explore the possibility of in vitro induction of cord blood cell-derived lymphocytes into cytotoxic T lymphocytes (CTL) with anti-leukemia specificity, umbilical cord blood (UCB)-derived mononuclear cells were cultured with multiple cytokines to generate dendritic cells (DC) in vitro. Leukemia cells were irradiated with (137)Cs and activated by premature cytokines. The characteristics of maturation of DC were evaluated through morphology examination and flow cytometry. DC pulsed with leukemic antigens were co-cultured with lymphocytes. Cytotoxicity of the CTL to corresponding leukemic cells was measured with lactate dehydrogenase-release assay. The results showed that UCB-derived monocytes could be induced into typical DC in all of the 12 samples. Expression of immunological markers such as CD1a(+), HLA-DR(+), CD86(+), CD83(+) on DC were significantly up-regulated (P < 0.05). DC presenting leukemic antigens generated leukemia-specific CTL with a killing rate of (44.76 +/- 17.42)% at the E:T ratio of 50:1 against AML cells and a killing rate of (8.50 +/- 4.25)% at the E:T ratio of 50:1 against ALL cells. Whereas, these CTL present almost no killing effect on the mononuclear cells collected from the same patients in complete remission phase. It is concluded that (1) it is possible to induce UCB-derived monocytes into mature DC with typical morphology. (2) Cord blood derived mature DC presenting leukemia antigen can generate leukemia-specific CTL with vigorous cytotoxic activity against the same leukemia blasts and low killing activity against bone marrow cells of the same patients in complete remission phase.
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PMID:Ex vivo induction of anti-leukemia cytotoxic T cell effect by dendritic cells from human umbilical cord blood cell origin. 1597 45

This study was aimed to investigate and compare the anti-leukemic effect mediated by dendritic cells (DC) derived from multidrug resistant (MDR) leukemia K562/A02 cells with high expression of p-glycoprotein (P-gp) and sensitive K562 cells. Multidrug resistant K562/A02 cell line and sensitive K562 cell line from chronic myeloid leukemia (CML) were induced for differentiating to DC in complete RPMI 1640 culture medium supplemented with GM-CSF (1 000 U/ml), IL-4 (500 U/ml) and TNF-alpha (100 ng/ml) for 14 days. The morphologic features of DC were observed by means of optical microscopy and the phenotype of DC was detected by flow cytometry. T-cell stimulating activity was determined by allogeneic lymphocyte reaction (allo-MLR). Cytotoxic activity was measured by MTT assay. The results indicated that DC derived from K562/A02 cells and K562 cells similarly showed the typical morphology of dendritic cell and expressed the surface differentiation antigens and costimulatory molecules CD1a, CD83, HLA-DR, CD80 and CD86 of DC. In allo-MLR, K562/A02-DC had a higher capacity to induce lymphocyte proliferation, compared with K562-DC (P < 0.05). K562/A02-DC and K562-DC could similarly generate specific cytotoxic activity against K562/A02 cells or K562 cells respectively, but low reactivity against HL-60 cells. More importantly, the cytotoxic activity mediated by K562/A02-DC was stronger than that by K562-DC against K562/A02 cells or HL-60/VCR cells (P < 0.01, respectively). It is concluded that functional DC can be differentiated from multidrug resistant leukemia K562/A02 cells as well as sensitive K562 cells in the presence of GM-CSF, IL-4 and TNF-alpha. Especially, DC derived from K562/A02 cells can induced a p-glycoprotein specific anti-leukemic immunity.
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PMID:[Induction of anti-leukemic immunity of dendritic cells derived from multidrug resistant leukemia K562/A02 cells with high expression of P-glycoprotein and sensitive K562 cells]. 1640 71

In chronic myeloid leukemia, bcr-abl+ monocytes provide a unique opportunity to generate dendritic cells (DC) expressing a broad spectrum of leukemic antigens, and bcr-abl+ DC vaccines may allow immunological eradication of leukemic cells persisting under treatment with the tyrosine kinase inhibitor imatinib. However, the efficiency of bcr-abl+ DC vaccines will critically depend on the absence of deleterious effects of bcr-abl and of imatinib on DC functions. We show that bcr-abl+ monocytes, devoid of contamination of CD14low granulocytic precursors, differentiate into DC with typical immunophenotypical and functional features, and bcr-abl transcription decreases simultaneously. During differentiation, imatinib induces a slight increase of DC apoptosis and prevents CD1a up-regulation in a dose-dependent manner in bcr-abl+ and normal monocyte-derived DC, but at most, 25% of DC fail to acquire CD1a. When DC maturation is induced in the presence of imatinib, bcr-abl+ and normal monocyte-derived DC up-regulate major histocompatibility complex and costimulatory molecules, CC chemokine receptor 7 and CD83. However, secretion of interleukin-12p70 is decreased in a dose-dependent manner. Imatinib exposure of bcr-abl+ and normal monocyte-derived DC during differentiation and maturation is not detrimental to T cell immunostimulatory functions of DC. In sharp contrast, imatinib, when added to DC-T cell cultures, profoundly suppresses DC-mediated T cell proliferation, despite reciprocal DC-T cell activation attested by up-regulation of CD25 on T cells and of CD86 on DC. Our findings demonstrate that T cells, not normal or bcr-abl+ monocyte-derived DC, are major targets for imatinib immunomodulatory effects. It can be envisioned already that imatinib-free windows will be required to enable vaccination-induced, leukemia-specific T cell expansion.
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PMID:Imatinib mesylate minimally affects bcr-abl+ and normal monocyte-derived dendritic cells but strongly inhibits T cell expansion despite reciprocal dendritic cell-T cell activation. 1646 46

This study was aimed to investigate the effects of tumor antigen-loaded dendritic cells (DC) stimulating the specific cytotoxic T lymphocytes (CTL) on Jurkat cells in vitro. Peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation from normal human heparinized blood, the adherent monocytes were cultured with granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-4 (IL-4), alpha tumor necrosis factor (TNF-alpha) and sCD40L, DCs were co-cultured with frozen-thawed antigen of Jurkat cells or WT1 peptides, and then T cells were triggered into specific CTL. The results showed that most suspended cells exhibited distinctive morphological features of DC which expressed CD40 (96%), CD86 (97%), CD80 (77%), CD1a (69%), and gained the powerful capacity to stimulate proliferation of allogeneic lymphocytes. Under the effector: target ratio of 20:1, CTLs derived from cultures with DC and frozen-thawed antigen of Jurkat cells showed 91.1% cytotoxicity against Jurkat cells, CTL derived from cultures with DC and WT1 peptides showed 87.5% cytotoxicity against Jurkat cells, cytotoxicity of CTL derived from cultures with unloaded DC against Jurkat cells was 42.1% and cytotoxicity of monocytes was 22.7%. Cytotoxicity of CTL derived from culture with frozen-thawed antigen or WT1 peptides loaded DC was stronger than that in control groups (P < 0.01). It is concluded that the tumor antigen-pulsed DC can induce efficient and specific anti-tumor immunity, may play a great role in clinical therapy for leukemia.
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PMID:[Antigen-loaded dendritic cells trigger killing effects of specific cytotoxic T lymphocytes on Jurkat cells in vitro]. 1692 24

In order to develop a protocol for clinical grade generation of dendritic cells (DCs) for cancer immunotherapy, aphereses were performed with the continuous flow cell separator and materials were derived from 10 leukemia patients that had achieved complete remission. Peripheral blood monocytes were cultured in vitro with GM-CSF, IL-4 for 6 days, then TNF-(the TNF-group) or TNF-, IL-1, IL-6, PGE2 (the cytokine mixture group) were added to promote maturation. Cell number was counted by hematology analyzer, and phenotype study (CD1a, CD14, CD83) was carried out by flow cytometry, and the function of DCs was examined by mixed lymphocyte reaction. The results showed that (0.70+/-0.13)x10(7)/mL (the TNF-alpha group) and (0.79+/-0.04)x10(7)/mL (the cytokine mixture group) DCs were generated respectively in peripheral blood obtained by leucapheresis. The phenotypes were as follows: CD1a+ (74.65+/-4.45)%, CD83+ (39.50+/-4.16)%, CD14+ (2.90+/-1.76)% in TNF-alpha group, and CD1a+ (81.86+/-5.87)%, CD83+ (81.65+/-6.36)%, CD14+ (2.46+/-1.68)% in the cytokine mixture group. It was concluded that leucapheresis may be a feasible way to provide large number of peripheral blood monocytes for DC generation, and combined administration of TNF-, IL-1, IL-6, and PGE2 may greatly promote maturity.
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PMID:Clinical grade of generation of dendritic cells for immunotherapy. 1764 38

A novel nude mice model of human extranodal nasal type NK/T-cell lymphoma was established by subcutaneously implanting the sample taken from the patient with secondary extranodal nasal type NK/T-cell lymphoma of the stomach into the right axillary region of a BALB/c (nu/nu) nude mouse. This model had been successfully transplanted in vivo for thirty-two generations with a stable growth cycle. The survival rates of both resuscitation and transplantation were 100%. Histologically, the tumor cells were medium to large size and arranged in sheets, with a little mesenchyma, and disseminated almost in all passages of the lymphoma-bearing nude mice. Immunologically, the tumor cells were positive for CD56, cytoplasmic CD3, granzyme B or TIA-1 and LMP1, sometimes for CD8 but negative for surface CD3, CD7, CD20 and CD1a. EBER1/2 was found. No T-cell receptor gamma gene rearrangement was detected in the transplanted tumors. Furthermore, both human sequencing-tagged sites SY14 and Y chromosome were detected by PCR or fluorescent in situ hybridization, respectively, in the transplanted tumor. The transplanted tumor in this novel nude mice model maintained the essential features of human extranodal nasal type NK/T-cell lymphoma, and it would be an ideal tool in vivo for further research of the tumor.
Leukemia 2008 Jan
PMID:A novel nude mice model of human extranodal nasal type NK/T-cell lymphoma. 1785 53

We report 2 patients with plasmacytoid dendritic cell leukemia (pDCL) expressing CD4, CD56, CD33, CD36, HLA-DR, CD123, CD86 and CD83 in the absence of lineage markers (myeloid, B, T or natural killer cells) except for CD33. Culturing leukemic blasts of both cases with IL-3 for 4 days increased the expression of surface molecules associated with antigen presentation, e.g. CD1a and CD40. Leukemic blasts of both cases possessed a considerable level of antigen-presenting ability to allogeneic lymphocytes in mixed leukocyte cultures. Culturing the blasts with IL-3 for 4 days markedly increased allogeneic antigen presenting ability. Combined with data showing evident graft-versus-leukemia effects without graft-versus-host disease in a cord blood stem cell transplanted pDCL case, leukemic cells in pDCL may act as potent antigen presenting cells in vivo, too.
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PMID:Plasmacytoid dendritic cell leukemia with potent antigen-presenting ability. 1894 86

This study was aimed to investigate the specific anti-leukemia cell effect of cytotoxic T lymphocytes (CTLs) induced by HL-60 or K562 cell-sensitized dendritic cells (DCs) from umbilical cord blood. 12 units of human umbilical cord blood (UCB) were collected and the mononuclear cells (MNCs) were isolated from UCB, then cultured with granulocyte monocyte colony- stimulating factor (GM-CSF), interleukin 3 (IL-3), recombinant human stem cell factor (SCF) and EPO for 3 - 4 weeks. Flow cytometry was used to determine the number of DCs and cell surface antigens before and after culture with monoclonal antibodies including CD83, CD1a, CD11c and CDw123. HL-60 and K562 were frozen-thawed, and released their tumor antigen peptides (TAP). The CTLs were produced by sensitizing T lymphocytes with DC-loaded HL-60 and K562 cell antigens. The test of (3)H-TdR incorporation was used to detect the immunostimulation activity of DCs. MTT assay was applied to evaluate specific cytotoxicity of CTL on leukaemia cells. The results indicated that the MNCs of UCBs cultured with GM-CSF, IL-3, EPO and SCF were shown to differentiate into CD1a(+) CD11c(+) CD83(+) CDw123(+) DCs. Numbers of DCs from UCBs remarkably increased in 2 - 4 weeks and then decreased. After culture with cytokines DCs increased (10.6 - 28.2) x 10(5)/ml in actual numbers. The CTL induced by DC pulsed with HL-60, K562 frozen-thawed lysates were effective to kill HL-60 and K562. Cytotoxicity of CTL to HL60 and K562 were (42.04 +/- 8.46)% and (31.25 +/- 11.07)% respectively. It is concluded that the MNCs of UCBs cultured with cytokines of GM-CSF, SCF, EPO and IL-3 can differentiate into CD1a(+), CD83(+), CD11c(+) and CDw123(+) DCs. The CTL induced by DCs pulsed with HL-60, K562 frozen-thawed lysates can effectively kill HL-60 and K562. These DCs as antigen presenting cells play an important role in cancer immunotherapy.
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PMID:[In vitro investigation on specific anti-leukemia cell effect of CTL induced by sensitized dendritic cells from umbilical cord blood]. 1937 83

This study was aimed to explore the effects of interleukin 21 (IL-21) on the anti-leukemia activity of cytotoxic T lymphocytes (CTL) induced by dendritic cells (DCs) in vitro. The peripheral mononuclear cells from leukemia patients in complete remission were cultured with the specific cytokines to induce the production of DCs. The DCs loaded with RNA from autologous leukemic cells as antigen, and co-cultured with autologous T lymphocytes to get leukemia specific CTL. The cytotoxic activity of CTL against autologous leukemic cells was measured by LDH release method. The concentration of IFN-gamma and TNF-alpha in the culture supernatant was measured by enzyme immunoassay. The effects of IL-21 on the mature DCs were also studied by the measurement of the phenotype of DC and the allogenic mixed lymphocytic reactions induced by DCs. Experiments were divided into 2 groups: test group in which IL-21 (200 ng/ml) was added in coculture of DC/CTL and control group in which no IL-21 (200 ng/ml) was added. The results showed that when cultured with IL-21, the quantity of CTL increased from (56.73 +/- 10.21)% (control group) to (73.43 +/- 18.01)% (p < 0.01); The concentration of IFN-gamma and TNF-alpha in the culture supernatant increased from (154.91 +/- 67.20) ng/L (control group) to (310.62 +/- 141.15) ng/L (p < 0.01) and from (8.77 +/- 5.09) microg/L (control group) to (15.25 +/- 6.56) microg/L (p < 0.01) respectively. At the effector: target ratio of 20:1, the cytotoxic activity against autologous leukemic cells by CTL increased from (50.22 +/- 5.07)% (control group) to (75.38 +/- 9.47)% (p < 0.01). IL-21 had neither effect on the phenotype (CD1a, CD83, CD86, CD80 and HLA-DR) of mature DCs nor the allogeneic mixed lymphocytic reactions induced by DCs. It is concluded that IL-21 can strengthen the proliferation of CTL, and improve the production of IFN-gamma and TNF-alpha, thus enhance the anti-leukemia activity of CTL. Nevertheless, there is no effect of IL-21 on the function of mature DCs. These data indicate that IL-21 has a potential clinical value in the enhancement of anti-leukemia immunotherapy.
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PMID:[Effects of interleukin 21 on anti-leukemia activity of cytotoxic T lymphocytes induced by dendritic cells]. 1954 77

Familial hemophagocytic lymphohistiocytosis is a rare, rapidly progressive disorder characterized by an activation of the immune system resulting in a systemic proliferation of lymphocytes and histiocytes. The disease is genetically heterogeneous and maps to at least 4 loci including the gene encoding perforin, a protein critical for the cytotoxic and regulatory functions of T lymphocytes and natural killer (NK) cells. Hepatic dysfunction often occurs early in the clinical course, but the pathology of the liver is not well characterized. The clinical history, laboratory data, and pathologic material (25 hepatic specimens) from 19 children (11 boys, 7 girls, 1 unknown, 12 d to 11 mo of age, median 3 mo) with FHL were reviewed. Routine and immunohistochemical stains were carried out in all cases, and perforin gene sequencing in a subset. Common to all specimens was a portal and sinusoidal infiltrate of CD3, CD8, granzyme B+ lymphocytes admixed with CD68, CD1a- histiocytes that exhibited hemophagocytosis. There was endothelialitis of portal and central veins and lymphocyte-mediated bile duct injury. The degree of portal and sinusoidal lymphohistiocytic infiltrate and endothelialitis varied from mild to marked and correlated with clinical severity. In some specimens, histiocytic cells predominated and in others, there was extensive hepatocellular giant cell transformation. Accordingly, 4 histopathologic patterns were observed: (1) chronic hepatitis-like, (2) leukemia-like, (3) histiocytic storage disorder-like, and (4) neonatal giant cell hepatitis-like. Two siblings homozygous for a 50delT nucleotide deletion had no perforin immunoreactive cells, 1 compound heterozygote for a deletion and missense mutation had cells with markedly diminished perforin expression, and 1 infant hemizygous for a perforin missense mutation had intact expression. Recognizing the morphologic changes in the liver and the immunophenotypic features of the infiltrate are critical for a rapid diagnosis and a prompt institution of treatment.
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PMID:Pathology of the liver in familial hemophagocytic lymphohistiocytosis. 2044 42


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