scholarly journals IL-17-Expressing CD4+and CD8+T Lymphocytes in Human Toxoplasmosis

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jéssica Líver Alves Silva ◽  
Karine Rezende-Oliveira ◽  
Marcos Vinicius da Silva ◽  
César Gómez-Hernández ◽  
Bethânea Crema Peghini ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Mononuclear Cells ◽  
Parasite Invasion ◽  
Cytokine Pattern ◽  
Cytokine Levels ◽  
Th1 And Th2 Cytokines ◽  
Tc17 Cells ◽  
And Control ◽  
Bead Arrays

This study aimed to measure the synthesis of Th1 and Th2 cytokines by mononuclear cells after culture with liveT. gondiiand identified Th17 (CD4+) and Tc17 (CD8+) cells in toxoplasma-seronegative and toxoplasma-seropositive parturient and nonpregnant women. Cytometric bead arrays were used to measure cytokine levels (IL-2, TNF-α, IFN-γ, IL-4, IL-5, and IL-10); immunophenotyping was used to characterize Th17 and Tc17 cells, and the cells were stained with antibodies against CD4+and CD8+T cells expressing IL-17. The addition of tachyzoites to cell cultures induced the synthesis of IL-5, IL-10, and TNF-αby cells from seronegative parturient women and of IL-5 and IL-10 by cells from seropositive, nonpregnant women. We observed a lower level of IL-17-expressing CD4+and CD8+T lymphocytes in cultures of cells from seronegative and seropositive parturient and nonpregnant women that were stimulated with tachyzoites, whereas analysis of the CD4+and CD8+T cell populations showed a higher level of CD4+T cells compared with CD8+T cells. These results suggest that the cytokine pattern and IL-17-expressing CD4+and CD8+T lymphocytes may have important roles in the inflammatory response toT. gondii, thus contributing to the maintenance of pregnancy and control of parasite invasion and replication.

scholarly journals Polyethylene Glycol-Conjugated Adenosine Deaminase (ADA) Therapy Provides Temporary Immune Reconstitution to a Child with Delayed-Onset ADA Deficiency

2005 ◽  
Vol 12 (7) ◽  
pp. 861-866 ◽  
Author(s):  
Elke Lainka ◽  
Michael S. Hershfield ◽  
Ines Santisteban ◽  
Pawan Bali ◽  
Annette Seibt ◽  
...  
Keyword(s):  
T Cells ◽  
Polyethylene Glycol ◽  
T Cell ◽  
Adenosine Deaminase ◽  
T Cell Activation ◽  
Immune Reconstitution ◽  
Mononuclear Cells ◽  
Interleukin 2 ◽  
Delayed Onset ◽  
Cytokine Levels

ABSTRACT We describe the effects of polyethylene glycol-conjugated adenosine deaminase (ADA) replacement therapy on lymphocyte counts, activation, apoptosis, proliferation, and cytokine secretion in a 14-month-old girl with “delayed-onset” ADA deficiency and marked immunodysregulation. Pretreatment lymphopenia affected T cells (CD4, 150/μl; CD8, 459/μl), B cells (16/μl), and NK cells (55/μl). T cells were uniformly activated and largely apoptotic (CD4, 59%; CD8, 82%); and T-cell-dependent cytokine levels in plasma were elevated, including the levels of interleukin 2 (IL-2; 26 pg/ml), IL-4 (81 pg/ml), IL-5 (46 pg/ml), gamma interferon (1,430 pg/ml), tumor necrosis factor alpha (210 pg/ml), and IL-10 (168 pg/ml). Mitogen-stimulated peripheral blood mononuclear cells show reduced IL-2 secretion and proliferation. During the first 5 months of therapy there was clinical improvement and partial immune reconstitution, with nearly normal lymphocyte subset numbers, reduced T-cell activation and CD4-cell apoptosis, and decreased plasma cytokine levels. In parallel, IL-2 secretion and the lymphocyte mitogenic response improved. Between 4 and 7 months, immunoglobulin G antibodies to bovine ADA developed and resulted in the complete reversal of immune recovery.

Phase I Trial of Adoptive Immunotherapy With Cytolytic T Lymphocytes Immunized Against a Tyrosinase Epitope

2002 ◽  
Vol 20 (4) ◽  
pp. 1075-1086 ◽  
Author(s):  
Malcolm S. Mitchell ◽  
Denise Darrah ◽  
David Yeung ◽  
Samuel Halpern ◽  
Anne Wallace ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Mononuclear Cells ◽  
Cytolytic T Lymphocytes ◽  
Intracellular Adhesion Molecule ◽  
Alive With Disease ◽  
Antigen Presenting ◽  
Hla A2.1 ◽  
Drosophila Cells

PURPOSE: To study distribution and toxicity of cytolytic T lymphocytes (CTLs) against a single melanoma epitope. PATIENTS AND METHODS: CD8+ T cells obtained by leukapheresis from 10 patients with disseminated HLA-A2.1+, tyrosinase-positive melanomas were immunized in vitro against tyrosinase369-377 (YMNGTMSQV). Drosophila cells transduced with HLA-A2.1, CD80, and CD54 (intracellular adhesion molecule-1) were used for priming, followed by two rounds of immunization with mononuclear cells as antigen-presenting cells. 1 × 108 CTL were infused intravenously (IV) on day 1. CTL frequency was measured by limiting dilutions in five patients. 111In labeling and scintigraphy measured distribution of CTL in next five. Five days later, 1 × 108 CTLs were infused on 4 successive days to both groups. Immunohistology of response was judged by biopsies. RESULTS: Infusions were nontoxic. CTLs were undetectable in the blood, going to lungs within 5 minutes. At 4, 24, and 72 hours, they were found in liver and spleen. Lesions were visualized by scintiscans in one responding patient where two subcutaneous nodules were noted at 4 and 24 hours. A second patient had a partial response and remains alive with disease 2 years later. CD8+ T cells were found in lesions of responders, associated with the presence of HLA-A2 molecules and tyrosinase. Two nonresponders without tyrosinase and HLA-A2 molecules had a paucity of CD8+ T cells in their lesions. Whether the CD8+ T cells in lesions of responders were those we had reinfused is uncertain. CONCLUSION: CTLs immunized against a single melanoma epitope were nontoxic but did not specifically localize to tumor sites. Nevertheless, two patients had disease regression. Additional therapeutic studies with specifically immunized CTL seem justified.

scholarly journals In vitro regulation of immunoglobulin synthesis after human marrow transplantation. II. Deficient T and non-T lymphocyte function within 3- 4 months of allogeneic, syngeneic, or autologous marrow grafting for hematologic malignancy

Blood ◽  
1982 ◽  
Vol 59 (4) ◽  
pp. 844-850 ◽  
Author(s):  
RP Witherspoon ◽  
LG Lum ◽  
R Storb ◽  
ED Thomas
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Mononuclear Cells ◽  
Hematologic Malignancy ◽  
Plaque Assay ◽  
Pokeweed Mitogen ◽  
Lymphocyte Function ◽  
Peripheral Blood Mononuclear ◽  
Immunoglobulin Secretion

Abstract Immunoglobulin secretion was studied in 37 patients between 19 and 106 days after allogeneic HLA-identical (30 patients), allogeneic one HLA- haplotype-identical (three patients), syngeneic (three patients), or autologous (one patient) marrow grafting. E rosette-positive (T) and E rosette-negative (non-T) peripheral blood mononuclear cells were cocultured with pokeweed mitogen for 6 days. Polyvalent immunoglobulin secretion was determined by counting plaque forming cells in a reverse hemolytic plaque assay. The number of antibody secreting cells in cocultures of autologous T and non-T lymphocytes was low in 40 of 44 tests conducted on samples from the 37 patients. Mononuclear or non-T cells from 38 of 40 tests failed to produce antibody when cultured with normal helper T cells. T cells from 23 of 37 tests failed to help normal non-T cells secrete antibody. T lymphocytes from 23 of 41 tests suppressed antibody production greater than 80% by normal T and non-T cells. The suppressor cells were radiosensitive in 17 of the 25 tests. The abnormal function of lymphocyte subpopulations in patients during the first 3 mo after syngeneic, allogeneic or autologous marrow grafting was similar regardless of the type of graft or the presence of acute graft versus host disease.

scholarly journals Cell-mediated suppression of megakaryocytopoiesis in acquired amegakaryocytic thrombocytopenic purpura

Blood ◽  
1986 ◽  
Vol 68 (3) ◽  
pp. 619-626 ◽  
Author(s):  
AM Gewirtz ◽  
MK Sacchetti ◽  
R Bien ◽  
WE Barry
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Lymphocytes ◽  
Colony Formation ◽  
Progenitor Cell ◽  
Mononuclear Cells ◽  
Platelet Glycoprotein ◽  
Severe Thrombocytopenia ◽  
Thrombocytopenic Purpura ◽  
Marrow Cells

Abstract Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a disorder of hematopoiesis characterized by severe thrombocytopenia due to a selective reduction or total absence of megakaryocytes in an otherwise normal-appearing bone marrow. Although the development of autoantibodies directed against cells in the megakaryocyte progenitor cell pool has been implicated in the pathogenesis of this disorder, cell-mediated suppression of megakaryocytopoiesis has not been described. Accordingly, we report two cases of AATP in which in vitro suppression of megakaryocyte colony formation by autologous ancillary marrow cells was demonstrable. Light-density bone marrow mononuclear cells (MNCs) obtained from both patients were either plated directly into plasma clot cultures, or after first being depleted by adherent monocytes (M phi) or T lymphocytes using standard methodologies. In some experiments, the depleted ancillary marrow cells were recovered for autologous co-culture studies with the MNCs from which they had been depleted. Megakaryocyte colony formation was detected in the cultures using an indirect immunofluorescence assay with a rabbit anti- human platelet glycoprotein antiserum. Removal of M phi (n = 6), or T lymphocytes (n = 4) from normal marrow MNCs had no apparent effect on colony formation. In contrast, depleting T lymphocytes from the MNCs of patient 1 significantly augmented megakaryocyte colony formation; a similar effect was observed after depleting M phi from the MNCs of patient 2. This observed augmentation in colony formation could be abrogated by autologous co-culture with the putative suppressor cell at effector cell/target cell ratios of 1:10 in the case of T lymphocytes or 1:5 in the case of M phi. Neither suppression nor stimulation of megakaryocyte colony formation was observed after culturing normal MNCs with autologous T cells (n = 4) or M phi (n = 3) at similar or greater ratios. We also observed inhibition of megakaryocyte colony formation after culturing normal MNCs in the presence of tissue culture medium conditioned by the M phi of patient 2. This effect was shown to be specific for megakaryocytes since this same conditioned medium had no significant effect on BFU-E and CFU-E-derived colony formation by autologous marrow mononuclear cells. These results suggest that: both T cells and M phi are capable of exerting a regulatory effect on the proliferation of human megakaryocyte progenitor cells (CFU-Meg); in the case of M phi, a soluble factor elaborated by these cells may be responsible for suppressing CFU-Meg growth; and aberrant ancillary cell- megakaryocyte progenitor cell interactions may lead to clinically significant disease.

scholarly journals Impact of Different Concentrations of Human Recombinant Growth Hormone on T Lymphocytes

2012 ◽  
Vol 25 (1) ◽  
pp. 87-97 ◽  
Author(s):  
P. Borrione ◽  
L. Grasso ◽  
M. Pautasso ◽  
A. Parisi ◽  
F. Quaranta ◽  
...  
Keyword(s):  
Growth Hormone ◽  
T Cells ◽  
T Lymphocytes ◽  
Mononuclear Cells ◽  
Th2 Response ◽  
Recombinant Growth Hormone ◽  
Growth Hormone Administration ◽  
Hormone Administration ◽  
Healthy Donors ◽  
Human Recombinant Growth Hormone

The aim of the present study is to evaluate the effects induced by increasing concentrations of human recombinant growth hormone on T lymphocytes. Ten healthy volunteers and twelve subjects with symptomatic allergies were enrolled in the study. Peripheral blood mononuclear cells and purified T lymphocytes were cultured in the presence of graded concentrations of growth hormone. Following appropriate in vitro stimulations, the proportion of apoptotic T cells, the percentage of activated T lymphocyte subpopulations, the phytohemagglutinin responsiveness and the Th2 response were assessed by flow cytometry analysis. Moreover, in order to evaluate the phosphoinositol-3-kinase signaling pathway involvement, cells were also analyzed after treatment with LY294002. The treatment with different concentrations of growth hormone did not influence the activation pattern of un-stimulated T lymphocytes. On the contrary, growth hormone was able to modify the CD38/HLA-DR co-expression of T cells activated with phytohemoagglutinin. A different response was observed when samples obtained from healthy donors and from subjects with symptomatic allergies were analysed. Moreover, growth hormone treatment was able to increase the Th2 response in the samples obtained from healthy donors only. The results of the present study strongly support the hypothesis that growth hormone administration may play an important role in conditions of impaired/activated immune systems. The observation that growth hormone administration at high doses may reverse its effects and that it may promote a Th2-oriented response have significant clinical implications when considering the use of this hormone for artificially enhancing the physical performances of healthy athletes.

scholarly journals A ricin A chain-containing immunotoxin that kills human T lymphocytes in vitro

Blood ◽  
1985 ◽  
Vol 66 (4) ◽  
pp. 908-912 ◽  
Author(s):  
PJ Martin ◽  
JA Hansen ◽  
ES Vitetta
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Protein Synthesis ◽  
T Lymphocytes ◽  
Mononuclear Cells ◽  
Ricin A Chain ◽  
Human T Lymphocytes ◽  
Blood Mononuclear Cells ◽  
A Chain ◽  
Ricin A

Abstract An immunotoxin specific for human T lymphocytes was prepared by coupling an IgG2a anti-CD3 murine monoclonal antibody (64.1) to purified ricin A chain (64.1-A). Treatment of blood mononuclear cells with this immunotoxin at a concentration of 1.7 X 10(-9) mol/L for two hours at 37 degrees C in the presence of 20 mmol/L NH4Cl decreased phytohemagglutinin-stimulated protein synthesis by 95%. In addition, a sensitive culture assay showed that fewer than 0.03% T cells remained after treatment of human bone marrow mononuclear cells with 64.1-A at a concentration of 1.7 X 10(-9) mol/L. The inhibition of protein synthesis could be prevented by preincubating cells with unconjugated 64.1 antibody but not by preincubating cells with a control IgG2a antibody that binds to a different T cell antigen (CD5). At concentrations up to 1 X 10(-8) mol/L, 64.1-A had little effect on blood mononuclear cells from baboons or human myeloid precursors (CFU- GM), which do not express the CD3 antigen recognized by 64.1. Taken together, these results indicate that the toxicity of 64.1-A was specific and that 64.1-A may be a useful reagent for depleting T cells from donor marrow as a means of preventing acute graft-v-host disease after allogeneic bone marrow transplantation.

IL-17-Producing T Cells Contribute to Mediate Acutegraft-Versus-Disease In Patients Undergoing Unmanipulated Blood and MarrowTransplantation

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2310-2310
Author(s):  
Xiang-Yu Zhao ◽  
Ling-Ling Xu ◽  
Sheng-Ye Lu ◽  
Kai-Yan Liu ◽  
Lan-Ping Xu ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Lymphocytes ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Acute Gvhd ◽  
Conflicts Of Interest ◽  
Tissue Injury ◽  
Tc17 Cells

Abstract Abstract 2310 Acute GVHD is a proinflammatory process mediated in part by mature donor T cells present in the stem cell or marrow inoculums that are polarized toward a Th1 phenotype and recognize minor or major histocompatibility disparities between the donor and host. A large amount of data has clearly shown that a newly identified subset of interleukin (IL)-17-producing CD4 T lymphocytes, named TH-17 cells, play a crucial role in triggering inflammation and tissue injury in various autoimmune diseases. The role of TH17 cells in acute GVHD had been controversial in recent mice and human transplantation. The aim of this study was to investigate the effects of IL17-producing T cells, including Th17 and Tc17 cells, on GVHD in patients receiving granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cell (PBPCs) and G-CSF-primed bone marrow (GBM) transplantation. Forty-one patients were analyzed according to the Th17 and Tc17 cell content in allograft in relation to aGVHD. Furthermore, ten patients with acute GVHD onset were monitored for the presence of Th17 cells by flow cytometry in the peripheral blood. Patients who subsequently developed aGVHD have greater proportions and doses of Th17 and Tc17 cells in GBM and PBPCs allograft infused into the patients (p=0.049 and 0.029 for Th17 in GBM; p=0.078 and p=0.033 for Tc17 in GBM; p=0.103 and 0.008 for Th17 in PBPCs; p=0.007 and 0.001 for Tc17 cells in PBPCs). At the same time, there were also significantly higher proportions and doses of Th1 and Tc1 cells in GBM and PBPCs allograft in patients with aGVHD compared with those levels in patients without aGVHD. Acute GVHD occurred 20 patients occurred, among which were 2 patients with gastrointestinal GVHD, 4 patients with skin plus gastrointestinal GVHD and the 14 others with simple skin GVHD. When we further compared patients according to the aGVHD target organ, we also found the significant association between dose of IL17 producing T cells (Th17 and Tc17) and the occurrence of simple skin GVHD. Cox regression models demonstrated that dose of Th17 in GBM (RR 1.095, CI 1.032– 1.162, P=0.003), dose of Tc17 in PBPCs (RR 1.063, CI 1.017– 1.112, P=0.008) and the number of HLA locus mismatch (RR 1.84, CI 1.18– 2.87, P=0.008) emerged as the independent factors influencing the occurrence of aGVHD. Patients receiving a higher dose of Th17 cells in GBM allograft (>8.5×104/kg, p=0.005), and Tc17 cells in PBPCs (>16.8×104/kg, p=0.001) exhibited a higher incidence of aGVHD. An increased Th17 population (up to 4.99% of CD4 T lymphocytes) was observed in patients with acute GVHD onset. In contrast, the percentage of Th17 cells drastically decreased in GVHD patients when they were treated to achieve partial and complete remission (p=0.013 and p=0.008, respectively). All percentages of Th17 and Tc17 were significantly reduced after G-CSF in vivo application. Our results suggest IL-17 producing T cells contribute to mediate aGVHD. Furthermore, G-CSF in vivo application helps to reduce the occurrence of aGVHD through reducing the secretion of IL17 in T cells. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Expression of Bcl-2 in Inflammatory Sites from Patients with Active Behçet's Disease

1999 ◽  
Vol 8 (2) ◽  
pp. 101-106 ◽  
Author(s):  
K. Hamzaoui ◽  
A. Hamzaoui ◽  
L. Zakraoui ◽  
A. Chabbou
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Behçet’S Disease ◽  
Messenger Rna ◽  
Behcet’S Disease ◽  
Mononuclear Cells ◽  
Behçet's Disease ◽  
Significant Proportion ◽  
Behcet's Disease ◽  
Hsv 1

Behçet's disease (BD) is a current systemic vasculitis of unknown aetiology. Eyes, skin, joints, the oral cavity, genital system, blood vessels, central nervous system and lung are usually involved. Defective regulation of programmed cell death (apoptosis) may play a role in the development of (BD), and the protooncogene Bcl-2 is involved in the control of apoptosis in immunocompetent cells. We therefore wished to investigate the expression of Bcl-2 in the peripheral lymphocytes and in two inflammatory sites of patients with active BD: bronchoalveolar lavage (BAL) and cerebrospinal fluid (CSF) lymphocytes. Levels of Bcl-2 expression in the lymphocytes of patients with BD and, for comparison, in the lymphocytes of healthy controls and non-inflammatory neurological diseases (NIND), were studied by two-colour cytofluorography and RNA analysis. In BD patients, a significant proportion of T cells expressed increased amounts of Bcl-2 protein, both in peripheral blood and in inflammatory sites. Mononuclear cells of patients with BD showed increased amount of Bcl-2 messenger RNA. The in vitro incubation of T lymphocytes with IL-10, significantly increased the Bcl-2 expression, specifically in T lymphocytes from inflammatory sites. In active BD, stimulation of HSV-1 T lymphocytes slightly increased Bcl-2 expression, not significantly different from unstimulated HSV-1 T cells. The occurrence of circulating T lymphocytes with abnormally high Bcl-2 expression in peripheral circulation and in inflammatory sites may be explained in part by the increasedin vivoactivation levels, and by aetiopathological agent(s): our findings seem to indicate an important role in the chronic inflammation in BD.

Depleting Autologous Activated CD4+ t Lymphocytes Increased Generation of Colony-Forming-Cells(CFC) in Patients with Myelodysplastic Syndromes

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5092-5092
Author(s):  
Zheng Zhang ◽  
Xiao Li ◽  
Qianqiao Zhang ◽  
Ying Tao ◽  
Qi He
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Mononuclear Cells ◽  
Fish Analysis ◽  
Low Grade ◽  
Healthy Donors ◽  
Magnetic Sorting ◽  
Colony Forming Cell

Abstract Objective To investigate how autoimmune mechanism playing a role in generation of colony-forming-cells(CFC), bone mononuclear cells(BMNC) from MDS were removed of autologous activated CD4+ T cells in vitro and cultured to find out effect of T cells on MDS hemopietic progenitor. Methods BMNC from 25 patients with low-grade MDS and 5 normal donors were depleted of CD4+CCR5+ T lymphocytes using magnetic sorting. Depleted and plused CD4+CCR5+ T BMNC were seeded onto methycellulose and the correlation of colony-forming-cell (CFC) number and the polarization of T cells were analyzed, the generation of CFC, the immunophenotype and the clonal cells(which had cytogenetic markers detected by FISH), was compared respectively. Results ¢Å The capacity of BMNC from 5 healthy donors to generate CFC remained unchanged in the CD4+CCR5+ T lymphocyte-depleted and lymphocyte-plused BMNC. In contrast, cultures initiated with CD4+CCR5+ T lymphocyte-depleted BMNC from patients with low-grade MDS exhibited significantly increased generation of CFC compared with the corresponding lymphocyte-plused cultures, but the lymphocyte-plused cultures had no generation of CFC. ¢Æ The number of CFU-E from the CD4+CCR5+ T lymphocyte-depleted BMNC from patients with low-grade MDS showed significantly correlation with the percentage of Th1 (r=0.52, p≤¼ 0.05), but had no correlation with the percentage of Tc1 and the rate of Th1/Th2 and Tc1/Tc2 (p >0.05); The number of CFC, CFU-G and CFU-GE had no correlation with the polarization of T lymphocyte (P >0.05). ¢Ç The percentage of CD34 in bone nucleated cells of low-grade MDS was higher than that in healthy donors(1.8% vs. 1.0%, P >0.05), that of CD33 in nucleated cells of low-grade MDS was significantly higher than that in healthy donors[(20.3±5.8)% vs.(13.8±1.8)%(P≤¼0.05)], and that of CD13 in nucleated cells of low-grade MDS was significantly higher than that in healthy donors[(21.1±6.4)% vs. (11.6±1.8)%(p<0.05)]. After cultivation, the percentage of CD34 in low-grade MDS nucleated cells decreased to 1.4%(P >0.05), that of CD33 decreased to (12.1±3.7)%(p<0.05), and that of CD13 decreased to (17.1±5.4)%(p<0.05), but the percentage of CD34, CD33 and CD13 had no significantly changed in healthy donors between pre-culture and post-culture. ¢È FISH analysis in 6 patients revealed that +8 clone was increased(from 51% to 61%), but 20q- and -7 clone cell had no significantly changed. Conclusion In certain subtypes of MDS, selectedly removement of autologous activated CD4T cells can increase the generation of colony-forming-cells(CFC) in vitro, and improve the differentiation of MDS medullary system, but the increased CFC consisting of residual normal hemopoiesis or conal hemopoiesis were still unconcluded.

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