scholarly journals CD4+ T Cell Profile and Activation Response in Sickle Cell Disease Patients with Osteonecrosis

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Paula B. Daltro ◽  
Tiago O. Ribeiro ◽  
Gildásio C. Daltro ◽  
Roberto J. Meyer ◽  
Vitor Fortuna
Keyword(s):  
T Cells ◽  
Sickle Cell Disease ◽  
Functional Status ◽  
Sickle Cell ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Cell Disease ◽  
Peripheral Blood Mononuclear ◽  
Differentiated Cells ◽  
Inflammatory Milieu

Recent evidence suggests that abnormalities involving CD4+T lymphocytes are associated with the pathophysiology of osteonecrosis (ON); however, few studies have addressed the CD4+T cells in ON related to sickle cell disease (SCD/ON). In addition, T cells producing multiple cytokines simultaneously are often present in the inflammatory milieu and may be implicated in the immune response observed in SCD/ON. In the present study, we aimed to characterize the functional status of CD4+T cells in SCD by simultaneously determining the frequency of IFN-γ+, IL-4+, and IL-17+ CD4+T in cell cultures under exogenous stimuli. Peripheral blood mononuclear cells (PB-MNCs) from 9 steady-state SCD patients, 15 SCD/ON patients, and 19 healthy controls had functional status of CD4+T cells analyzed. Bone marrow mononuclear cells (BM-MNCs) from 24 SCD/ON patients (SCD BM) and 18 patients with ON not related to SCD (non-SCD BM) were also analyzed. We found that PB-MNC of SCD patients with or without ON presented significantly reduced TCD4+, TCD8+, and TCD4+ naïve cell frequencies and increased frequency of circulating CD4+T cells able to simultaneously produce IFN-γ+/IL4+ and IL-17+/IL4+ compared to healthy controls. Conversely, the polyclonal stimulation of BM-MNC induced an increased frequency of CD4+IFN-γ+ and CD4+IL-17+ in SCD BM compared to non-SCD BM. The increased proportion of CD4+ T cells able to produce a broad spectrum of proinflammatory cytokines after a strong stimulus indicates that the immune system in SCD/ON patients presents an expressive pool of partially differentiated cells ready to take on effector function. It is possible that this increased subpopulation may extend to inflammatory sites of target organs and may contribute to the maintenance of inflammation and the pathophysiology of osteonecrosis in sickle cell disease.

scholarly journals Interferon Induction By HbS, SERINC5 Upregulation and Reduction of HIV-1 Nef and AP2 Contribute to HIV-1 Restriction in Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 5-6
Author(s):  
Namita Kumari ◽  
Marina Jerebtsova ◽  
Songping Wang ◽  
Sharmin Diaz ◽  
Sergei Nekhai
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Interferon Response ◽  
Cell Disease ◽  
Restriction Factors ◽  
Peripheral Blood Mononuclear ◽  
Hiv 1

Concerted action of numerous positively acting cellular factors is essential for Human immunodeficiency virus type 1 (HIV-1) replication but in turn is challenged by anti-viral restriction factors. Previously we showed that ex vivo one round HIV-1 replication and replication of fully competent T-tropic HIV-1(IIIB) is significantly reduced in peripheral blood mononuclear cells (PBMCs) obtained from patients with Sickle Cell Disease (SCD). Further, we identified and confirmed CDKN1A (p21) and CH25H as host restriction factors expressed in SCD PBMCs that may contribute to the HIV-1 inhibition, in addition to the previously reported SAMHD1 and IKBα. Since CH25H is an interferon stimulated gene (ISG), we analyzed IRFs and interferon expression in SCD PBMCs. Higher levels of IRF7 and IFNβ mRNA were observed in SCD PBMCs compared to controls. We probed further to ascertain if hemin or sickle Hb was responsible for interferon response. We found upregulation of IFNβ in THP-1 - derived macrophages treated with lysates of HbSS RBCs or purified HbS as compared to untreated or HbA treated controls. HbSS RBCs lysates and purified HbS inhibited HIV-1 gag mRNA expression in monocyte-derived macrophages infected with HIV-1(Ba-L). Recent clinical study showed increased levels of CD4 in HIV-1 infected SCD patients in Africa. Thus we analyzed CD4 levels in HIV-1 IIIB infected SCD PBMCs, and found them to be higher compared to controls. Levels of HIV-1 nef mRNA, that controls CD4 expression was lower in HIV-1 IIIB infected SCD PBMCs. As Nef counteracts SERINC3/5 restriction factor, we analyzed its expression as well as the expression of AP2 clathrin adaptor that is required for Nef mediated internalization of CD4. AP2 expression was lower and SERINC5 expression was higher in SCD PBMCs. CONCLUSIONS: SCD PBMCs could resist HIV-1 infection because of the increased IFNβ production by macrophages exposed to HbSS or sickle cell RBCs. SCD PBMC have increased levels of SERNIC5 and lower levels of HIV-1 Nef and host AP2 expression that, culumlatively, can increased CD4 levels and lead to the overall improved immunological health of SCD patients. ACKNOWLEDGMENTS: This work was supported by NIH Research Grants (1P50HL118006, 1R01HL125005, 1SC1HL150685, 5U54MD007597, 1UM1AI26617 and P30AI087714). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Disclosures No relevant conflicts of interest to declare.

Inhibition of HIV-1 in Sickle Cell Disease Peripheral Blood Mononuclear Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1509-1509
Author(s):  
Tatiana Ammosova ◽  
Sharroya Charles ◽  
Jamie Rotimi ◽  
Altreisha Foster ◽  
Sharmin Diaz ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cell Disease ◽  
Peripheral Blood Mononuclear ◽  
Regulatory Subunits ◽  
Blood Mononuclear Cells ◽  
Hiv 1

Abstract Abstract 1509 Poster Board I-532 Background The hypoxic response is an important component of the body 's reaction to impaired tissue oxygenation associated with the anemia and vasoocclusive episodes of sickle cell disease (SCD). It has been reported that HIV infection progresses relatively slowly in patients with SCD (Am J Hematol 1998; 59:199-207). We recently showed that HIV-1 transcription and replication is significantly reduced in cells cultured at 3% versus 21% oxygen (J Cell Physiol 2009; in press). Our previous studies indicated that protein phosphatase-1 (PP1) interacts with HIV-1 transcriptional activator, Tat, and thereby participates in the regulation of HIV-1 transcription. Sickle cell patients are in chronically hypoxic state and we hypothesized that HIV-1 replication in their peripheral blood mononuclear cells (PBMCs) would be slower then in controls. Methods We isolated PBMCs from patients with SCD and from normal subjects, activated the cells with phytohemagglutinin and IL-2 for 24 h, and infected with pseudotyped HIV-1 virus expressing Luciferase. The infected cells were cultured at 3% of oxygen for 72 h. Results We show here that PP1 association with cellular regulatory subunits is modified and that PP1 activity is significantly reduced by 20-40% in different cell lines at 3% versus 21% oxygen. One round of replication of pseudotyped HIV-1 Luciferase virus normalized to the number of the cells in culture was significantly reduced in SCD PBMCs comparing to normal controls. Conclusions Our results provide a direct evidence of that HIV-1 replication may be slower in SCD-derived PBMCs. In future, we will analyze PP1 activity and the association of PP1 with regulatory subunits in SCD PBMCs. Understanding of how oxygen status influences HIV-1 replication might open new possibilities for treatment of hidden HIV-1 reservoirs that harbor non-replicating HIV-1 virus. Acknowledgments This work was supported by NHLBI Research Grant 2 R25 HL003679-08 from the National Institutes of Health and The Office of Research on Minority Health. Disclosures No relevant conflicts of interest to declare.

scholarly journals Placenta growth factor induces 5-lipoxygenase–activating protein to increase leukotriene formation in sickle cell disease

Blood ◽  
2009 ◽  
Vol 113 (5) ◽  
pp. 1129-1138 ◽  
Author(s):  
Nitin Patel ◽  
Caryn S. Gonsalves ◽  
Minyang Yang ◽  
Punam Malik ◽  
Vijay K. Kalra
Keyword(s):  
Growth Factor ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Mononuclear Cells ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Nuclear Factor Κb ◽  
Airway Hyperreactivity ◽  
Cell Disease ◽  
Placenta Growth Factor ◽  
Peripheral Blood Mononuclear

Abstract Individuals with sickle cell disease (SCD) have increased inflammation, a high incidence of airway hyperreactivity (AH), and increased circulating leukotrienes (LT). We show that expression of 5-lipoxygenase and 5-lipoxygenase activating protein (FLAP), key catalytic molecules in the LT pathway, were significantly increased in peripheral blood mononuclear cells (MNCs) in patients with SCD, compared with healthy controls. Placenta growth factor (PlGF), elaborated from erythroid cells, activated MNC and THP-1 monocytic cells to induce LT production. PlGF-mediated increased FLAP mRNA expression occurred via activation of phosphoinositide-3 (PI-3) kinase, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and hypoxia inducible factor-1α (HIF-1α). HIF-1α small interfering RNA (siRNA) reduced PlGF-induced FLAP expression. FLAP promoter-driven luciferase constructs demonstrated that PlGF-mediated luciferase induction was abrogated upon mutation of HIF-1α response element (HRE), but not the nuclear factor-κB (NF-κB) site in the FLAP promoter; a finding confirmed by chromatin immunoprecipitation (ChIP) analysis. PlGF also increased HIF-1α binding to the HRE in the FLAP promoter. Therefore, it is likely that the intrinsically elevated levels of PlGF in SCD subjects contribute to increased LT, which in turn, mediate both inflammation and AH. Herein, we identify a mechanism of increased LT in SCD and show HIF-1α as a hypoxia-independent target of PlGF. These studies provide new avenues to ameliorate these complications.

Placenta growth factor activates monocytes and correlates with sickle cell disease severity

Blood ◽  
2003 ◽  
Vol 102 (4) ◽  
pp. 1506-1514 ◽  
Author(s):  
Natalya Perelman ◽  
Suresh K. Selvaraj ◽  
Sandeep Batra ◽  
Lori R. Luck ◽  
Anat Erdreich-Epstein ◽  
...  
Keyword(s):  
Steady State ◽  
Growth Factor ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Mononuclear Cells ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Erythroid Cells ◽  
Cell Disease ◽  
Placenta Growth Factor

Abstract Sickle cell disease (SCD) results in chronic hypoxia and secondarily increased erythropoietin concentrations. Leukocytosis and activated monocytes are also observed in SCD in absence of infection or vaso-occlusion (steady state), the reasons for which are unknown. We found that erythroid cells produced placenta growth factor (PlGF), an angiogenic growth factor belonging to the vascular endothelial growth factor (VEGF) family, and its expression was induced in bone marrow CD34+ progenitor cells in the presence of erythropoietin. Furthermore, the steady state circulating PlGF levels in subjects with severe SCD (at least 3 vaso-occlusive crises [VOCs] per year) were 18.5 ± 1.2 pg/mL (n = 9) compared with 15.5 ± 1.2 pg/mL (n = 13) in those with mild SCD (fewer than 3 VOCs per year) and 11.3 ± 0.7 pg/mL (n = 9) in healthy controls (P < .05), suggesting a correlation between PlGF levels and SCD severity. In addition, PlGF significantly increased mRNA levels of the proinflammatory cytochemokines interleukin-1β, interleukin-8, monocyte chemoattractant protein-1, and VEGF in peripheral blood mononuclear cells (MNCs) of healthy subjects (n = 4; P < .05). Expression of these same cytochemokines was significantly increased in MNCs from subjects with SCD at steady state (n = 14), compared with healthy controls. Of the leukocyte subfractions, PlGF stimulated monocyte chemotaxis (P < .05, n = 3). Taken together, these data show for the first time that erythroid cells intrinsically release a factor that can directly activate monocytes to increase inflammation. The baseline inflammation seen in SCD has always been attributed to sequelae secondary to the sickling phenomenon. We show that PlGF contributes to the inflammation observed in SCD and increases the incidence of vaso-occlusive events.

In vitro Antibody Synthesis by Peripheral Blood Mononuclear Cells from Patients with Sickle Cell Disease

1990 ◽  
Vol 84 (2) ◽  
pp. 89-94 ◽  
Author(s):  
Inés Malavé ◽  
Edgar Escalona ◽  
Yolanda Perdomo ◽  
Marisol Pocino ◽  
David Malavé ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cell Disease ◽  
Antibody Synthesis ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

scholarly journals Sickle Cell Disease Activates Peripheral Blood Mononuclear Cells to Induce Cathepsins K and V Activity in Endothelial Cells

Anemia ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Philip M. Keegan ◽  
Sindhuja Surapaneni ◽  
Manu O. Platt
Keyword(s):  
Endothelial Cells ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cathepsin K ◽  
Cell Disease ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Sickle cell disease is a genetic disease that increases systemic inflammation as well as the risk of pediatric strokes, but links between sickle-induced inflammation and arterial remodeling are not clear. Cathepsins are powerful elastases and collagenases secreted by endothelial cells and monocyte-derived macrophages in atherosclerosis, but their involvement in sickle cell disease has not been studied. Here, we investigated how tumor necrosis alpha (TNFα) and circulating mononuclear cell adhesion to human aortic endothelial cells (ECs) increase active cathepsins K and V as a model of inflammation occurring in the arterial wall. ECs were stimulated with TNFα and cultured with peripheral blood mononuclear cells (PBMCs) from persons homozygous for sickle (SS) or normal (AA) hemoglobin. TNFα was necessary to induce cathepsin K activity, but either PBMC binding or TNFα increased cathepsin V activity. SS PBMCs were unique; they induced cathepsin K in ECs without exogenous TNFα (n=4,P<0.05). Inhibition of c-Jun N-terminal kinase (JNK) significantly reduced cathepsins K and V activation by 60% and 51%, respectively. Together, the inflammation and activated circulating mononuclear cells upregulate cathepsin activity through JNK signaling, identifying new pharmaceutical targets to block the accelerated pathology observed in arteries of children with sickle cell disease.

Alterations In Specific Immune Cell Subsets In Children With Sickle Cell Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2208-2208 ◽  
Author(s):  
Robert S. Nickel ◽  
Jeanne E. Hendrickson ◽  
John T. Horan ◽  
Aneesah P. Garrett ◽  
Jennifer M. Robertson ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Sickle Cell Disease ◽  
Nk Cells ◽  
Sickle Cell ◽  
Immune Cell ◽  
Effector Memory ◽  
Cell Populations ◽  
Healthy Controls ◽  
Cell Disease

Abstract Introduction Patients with sickle cell disease (SCD) are known to have altered immune systems. In the past, immunology studies in SCD patients have focused largely on splenic dysfunction and the increased risk of infection with encapsulated organisms. Increasingly, however, it is now being recognized that SCD patients also have evidence of abnormal immune activation with baseline chronic inflammation as well as high rates of red blood cell (RBC) alloimmunization and hematopoietic stem cell transplant (HSCT) graft rejection. We have previously demonstrated an increased risk of bone marrow transplant rejection with non-myeloablative conditioning in a SCD mouse model, with both increased T cells and natural killer (NK) cells implicated in this rejection. We have also previously shown that at baseline children with SCD have altered immune cell subsets. We now have expanded on this investigation of quantitative immune deviation in pediatric SCD by exploring how chronic transfusion (CT) or hydroxyurea (HU) therapy affects immunophenotype in a larger cohort of patients. Methods One hundred and eleven children (68 patients on CT only, 26 patients on HU only, 17 patients on neither CT nor HU) with SCD (SS or Sβ0) and 29 healthy, age-matched African American controls were recruited for this study. Exclusion criteria included recent illness or another disease associated with known abnormalities of the immune system. Flow cytometry was performed on samples from all participants to quantify the following immune cell populations: total white blood cells (WBC), total monocytes, total lymphocytes, T cells (total, CD4+, CD8+, naïve, central memory, effector memory, effector memory RA, and CD4+ T regulatory), B cells (total, naïve, and memory) and NK cells. Results SCD patients on CT and patients not receiving CT or HU (no CT/HU) had significantly increased total WBCs, granulocytes, monocytes, lymphocytes, T cells and B cells compared to healthy controls. Conversely, while SCD patients on HU also had mean counts that were elevated, they were not significantly greater than controls for any of these cell populations (Figure 1). Similarly, CD4+ T cells were significantly increased only in the CT and no CT/HU patients compared to controls (Figure 2). CD8+ T cells, however, were increased only in the CT group. CD4+ T cell subset analysis showed the most striking elevations in the CD4+ central memory and CD4+ effector memory (TEM) populations for both CT and no CT/HU patients compared to controls (Figure 3). CD4+ T regulatory cells were also increased in both of these groups. B cell analysis showed increased numbers of naïve but not memory B-cells in CT and no CT/HU patients. In distinct contrast to most populations that were elevated in CT patients, cytotoxic NK cells were uniquely increased only in no CT/HU patients. Conclusions Children with SCD have quantitative differences in many different immune cell populations compared to age and race matched healthy controls. HU treatment appears to bring the absolute number of these cell subsets closer to those of healthy controls, while CT does not. It is unclear at this point to what extent CT therapy itself or baseline patient characteristics leading to the need for CT contribute to these findings. Future work is investigating whether certain cell subset abnormalities are associated with particular therapeutic complications such as RBC alloimmunization or HSCT graft rejection. Better understanding the immunology of SCD may allow for targeted therapies to improve SCD transfusion support and HSCT outcomes. Disclosures: Off Label Use: Abstract includes information related to the use of hydroxyurea in children with sickle cell disease.

scholarly journals Paraoxonases (PON) 1, 2, and 3 Polymorphisms and PON-1 Activities in Patients with Sickle Cell Disease

Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 252 ◽  
Author(s):  
Cadiele Oliana Reichert ◽  
Carolina Garcia de Macedo ◽  
Débora Levy ◽  
Bruno Carnevale Sini ◽  
Andréia Moreira Monteiro ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Protective Factor ◽  
Plasma Cholesterol ◽  
Transferrin Saturation ◽  
Density Lipoprotein ◽  
Ldl Oxidation ◽  
Healthy Controls ◽  
Cell Disease ◽  
Q192r Polymorphism

(1) Background: Oxidative stress, chronic inflammation, vasoocclusion, and free iron are all features present in sickle cell disease. Paraoxonases (PON) are a family (PON-1, PON-2, PON-3) of antioxidant enzymes with anti-inflammatory action. Here, for the first time, we described PON-1 activities and PON-1, PON-2, PON-3 polymorphisms in patients with sickle cell disease, homozygous for HbSS, compared with healthy controls. (2) Methods: The groups were matched for age and gender. PON-1 activities (arylesterase and paraoxonase) were determined by enzymatic hydrolysis of phenylcetate and paraoxon, respectively. Polymorphisms were determined by Restriction Fragment Length Polymorphism- Polymerase Chain Reaction (RFLP-PCR). (3) Results: Plasma cholesterol and fractions, ApoA1 and ApoB levels were all decreased in sickle cell disease patients, while anti-oxidized low-density lipoprotein (LDL) antibodies and C-reactive protein were increased. Serum arylesterase activity was lower in sickle cell disease patients when compared with healthy controls. In patients, paraoxonase activity was higher in those with PON-1 RR Q192R polymorphism. In these patients, the increase of serum iron and ferritin levels and transferrin saturation were less pronounced than those observed in patients with QQ or QR polymorphism. No differences were observed with PON-1 L55M, and PON-2 and PON-3 polymorphisms. Multivariate regression analysis showed that transferrin and ferritin concentrations correlated with arylesterase and paraoxonase activities. (4) Conclusions: Both transferrin and ferritin were the main predictors of decreased arylesterase and paraoxonase activities in patients with sickle cell disease. LDL oxidation increased, and RR PON-1 Q192R polymorphism is likely to be a protective factor against oxidative damage in these patients.

scholarly journals Serum Iron Levels and Copper-to-Zinc Ratio in Sickle Cell Disease

Medicina ◽  
2019 ◽  
Vol 55 (5) ◽  
pp. 180
Author(s):  
Charles Antwi-Boasiako ◽  
Gifty Dankwah ◽  
Robert Aryee ◽  
Charles Hayfron-Benjamin ◽  
Alfred Doku ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Serum Levels ◽  
Zinc Homeostasis ◽  
Healthy Controls ◽  
Cell Disease ◽  
Flame Atomic Absorption ◽  
Iron Copper ◽  
Copper And Zinc

Background and Objectives: Altered copper and zinc homeostasis may influence the antioxidant defense system and consequently lead to oxidative stress and associated complications in sickle cell disease (SCD) patients. Iron levels have been reported to increase in sickle cell patients due to frequent blood transfusion, chronic intravenous haemolysis and increased absorption of iron from the gastrointestinal tract. These elevated levels of iron may also lead to extensive oxidative damage. The current study evaluated serum levels of iron, copper and zinc in SCD patients and “healthy” controls. Materials and Methods: The study was a cross-sectional one, comprising 90 SCD patients with Haemoglobin SS and Haemoglobin SC genotypes and 50 HbAA “healthy” controls. Serum levels of iron, copper and zinc were measured using a Flame Atomic Absorption Spectrometer (Variant 240FS manufactured by VARIAN Australia Pty Ltd, VIC, Australia). Copper and zinc ratios were calculated and analyzed. Results: Serum levels of iron and copper were significantly elevated in the SCD patients, compared to their “healthy” counterparts (p < 0.001). These levels were further increased in patients with haemoglobin SS in vaso-occlusive crises (HbSS VOCs). Serum zinc levels were, however, significantly lower in the SCD patients, particularly during vaso-occlusion. The copper-to-zinc ratio was also found to be significantly higher in the SCD patients. Conclusion: Elevated copper-to-zinc ratio may be a biomarker of sickle cell oxidative stress and associated complications. The ratio may also be informative for the management of sickle cell oxidative burden. The significantly lower levels of zinc in the SCD patients may warrant zinc supplementation.

scholarly journals Different Profile of Interleukin-10 Production in Circulating T Cells from Atopic Asthmatics Compared with Healthy Subjects

2004 ◽  
Vol 11 (1) ◽  
pp. 33-38 ◽  
Author(s):  
K Matsumoto ◽  
S Narita ◽  
T Rerecich ◽  
DP Snider ◽  
PM O'Byrne
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
Healthy Subjects ◽  
Mononuclear Cells ◽  
Interleukin 10 ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Circulating T Cells ◽  
Normal Controls

BACKGROUND:Interleukin (IL)-10 is a pleiotropic cytokine released from various cells, including T cells. Although IL-10 is suggested to inhibit allergic responses, its role in asthma remains uncertain. The purpose of the present study was to compare the profile of IL-10 in circulating T cells from stable atopic asthmatics, atopic nonasthmatics and healthy controls.METHODS:Peripheral blood mononuclear cells were isolated, stained with anti-CD3 and CD4/CD8 antibodies, and then processed for intracellular IL-10 detection by flow cytometry.RESULTS:A kinetic study in healthy controls showed that stimulation with phorbol 12-myristate 13-acetate and ionomycin significantly increased the frequencies of IL-10-producing CD3+, CD4+and CD8+cells. Without stimulation, the frequencies of IL-10-producing CD3+, CD4+and CD8+cells were significantly higher in asthmatics than in healthy controls, while a similar trend was observed in atopic nonasthmatics. Stimulation for 24 h significantly increased IL-10-producing CD3+, CD4+and CD8+cells in healthy controls and atopic nonasthmatics, but not in asthmatics.CONCLUSIONS:The frequency of IL-10-producing T cells is increased in the circulation of stable atopic asthmatics compared with normal controls. The lack of enhancement in their frequency by phorbol 12-myristate 13-acetate and ionomycin in asthmatics suggests that the circulating T cells of asthmatic subjects are maximally stimulated with regards to IL-10 production; alternatively, IL-10 production by T cells from asthmatics may be regulated differently than T cells from other subjects.

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