scholarly journals Increased Frequency of Regulatory T Cells and T Lymphocyte Activation in Persons with Previously Treated Extrapulmonary Tuberculosis

2011 ◽  
Vol 19 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Alexandre S. de Almeida ◽  
Christina T. Fiske ◽  
Timothy R. Sterling ◽  
Spyros A. Kalams
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Pulmonary Tuberculosis ◽  
Treg Cell ◽  
T Lymphocyte ◽  
Extrapulmonary Tuberculosis ◽  
Lymphocyte Activation ◽  
Content Type ◽  
T Lymphocyte Activation ◽  
Previously Treated

ABSTRACTExtrapulmonary tuberculosis may be due to underlying immune compromise. Immunosuppressive regulatory T cells (Treg cells), and CD4+T lymphocytes in general, are important in the host immune response toMycobacterium tuberculosis. We evaluated T lymphocytes from patients after recovery from extrapulmonary tuberculosis, which may reflect conditions beforeM. tuberculosisinfection. A case-control study was conducted among HIV-uninfected adults with previously treated extrapulmonary tuberculosis and 3 sets of controls: (i) subjects with previously treated pulmonary tuberculosis, (ii) close tuberculosis contacts withM. tuberculosisinfection, and (iii) close tuberculosis contacts with no infection. Monocyte-depleted peripheral blood mononuclear cells (PBMC-M) were stained for CD4+CD25hiCD127lowFoxP3+cell (Treg cell) and T lymphocyte activation. Both characteristics were compared as continuous variables between groups with the Kruskal-Wallis test. There were 7 extrapulmonary tuberculosis cases, 18 pulmonary tuberculosis controls, 17 controls withM. tuberculosisinfection, and 18 controls withoutM. tuberculosisinfection. The median Treg cell proportion was highest among persons with previous extrapulmonary tuberculosis (1.23%) compared to subjects with pulmonary tuberculosis (0.56%), latentM. tuberculosisinfection (0.14%), or noM. tuberculosisinfection (0.20%) (P= 0.001). The median proportion of CD4+T lymphocytes that expressed the activation markers HLA-DR and CD38 was highest for CD4+T lymphocytes from persons with previous extrapulmonary tuberculosis (0.79%) compared to subjects with pulmonary tuberculosis (0.44%), latentM. tuberculosisinfection (0.14%), or noM. tuberculosisinfection (0.32%) (P= 0.005). Compared with controls, persons with previously treated extrapulmonary tuberculosis had the highest Treg cell frequency, but also the highest levels of CD4+T lymphocyte activation. Immune dysregulation may be a feature of individuals at risk for extrapulmonary tuberculosis.

scholarly journals Dynamics of T-Lymphocyte Activation Related to Paradoxical Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome in Persons With Advanced HIV

2021 ◽  
Vol 12 ◽  
Author(s):  
Rafael Tibúrcio ◽  
Beatriz Barreto-Duarte ◽  
Gopolan Naredren ◽  
Artur T. L. Queiroz ◽  
Selvaraj Anbalagan ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Lymphocyte Activation ◽  
Art Initiation ◽  
T Lymphocyte Activation ◽  
Inflammatory Syndrome

Most persons living with HIV (PLWH) experience a significant restoration of their immunity associated with successful inhibition of viral replication after antiretroviral therapy (ART) initiation. Nevertheless, with the robust quantitative and qualitative restoration of CD4+ T-lymphocytes, a fraction of patients co-infected with tuberculosis develop immune reconstitution inflammatory syndrome (TB-IRIS), a dysregulated inflammatory response that can be associated with significant tissue damage. Several studies underscored the role of adaptive immune cells in IRIS pathogenesis, but to what degree T lymphocyte activation contributes to TB-IRIS development remains largely elusive. Here, we sought to dissect the phenotypic landscape of T lymphocyte activation in PLWH coinfected with TB inititating ART, focusing on characterization of the profiles linked to development of TB-IRIS. We confirmed previous observations demonstrating that TB-IRIS individuals display pronounced CD4+ lymphopenia prior to ART initiation. Additionally, we found an ART-induced increase in T lymphocyte activation, proliferation and cytotoxicity among TB-IRIS patients. Importantly, we demonstrate that TB-IRIS subjects display higher frequencies of cytotoxic CD8+ T lymphocytes which is not affected by ART. Moreover, These patients exhibit higher levels of activated (HLA-DR+) and profilerative (Ki-67+) CD4+ T cells after ART commencenment than their Non-IRIS counterparts. Our network analysis reveal significant negative correlations between Total CD4+ T cells counts and the frequencies of Cytotoxic CD8+ T cells in our study population which could suggest the existance of compensatory mechanisms for Mtb-infected cells elimination in the face of severe CD4+ T cell lymphopenia. We also investigated the correlation between T lymphocyte activation profiles and the abundance of several inflammatory molecules in plasma. We applied unsupervised machine learning techniques to predict and diagnose TB-IRIS before and during ART. Our analyses suggest that CD4+ T cell activation markers are good TB-IRIS predictors, whereas the combination of CD4+ and CD8+ T cells markers are better at diagnosing TB-IRIS patients during IRIS events Overall, our findings contribute to a more refined understanding of immunological mechanisms in TB-IRIS pathogenesis that may assist in new diagnostic tools and more targeted patient management.

scholarly journals Systemic and Mucosal T-Lymphocyte Activation Induced by Recombinant Adenovirus Vaccines in Rhesus Monkeys

2009 ◽  
Vol 83 (20) ◽  
pp. 10596-10604 ◽  
Author(s):  
Yue Sun ◽  
Robert T. Bailer ◽  
Srinivas S. Rao ◽  
John R. Mascola ◽  
Gary J. Nabel ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Rhesus Monkeys ◽  
Recombinant Adenovirus ◽  
Lymphocyte Activation ◽  
T Cell Responses ◽  
Cell Responses ◽  
T Lymphocyte Activation

ABSTRACT The administration of vectors designed to elicited cell-mediated immune responses may have other consequences that are clinically significant. To explore this possibility, we evaluated T-cell activation during the first 2 months after recombinant adenovirus serotype 5 (rAd5) prime or boost immunizations in rhesus monkeys. We also evaluated the kinetics of T-lymphocyte activation in both the systemic and the mucosal compartments after rAd5 administration in monkeys with preexisting immunity to Ad5. The rAd5 immunization induced lower-frequency Gag epitope-specific CD8+ T cells in the colonic mucosa than in the peripheral blood. There was evidence of an expansion of the simian immunodeficiency virus Gag-specific CD8+ T-cell responses, but not the Ad5 hexon-specific T-cell responses, following a homologous rAd5 boost. A striking but transient T-lymphocyte activation in both the systemic and the mucosal compartments of rhesus monkeys was observed after rAd5 immunization. These findings indicate that the administration of a vaccine vector such as Ad5 can induce a global activation of T cells.

scholarly journals Shikonin Suppresses Human T Lymphocyte Activation through Inhibition of IKKβActivity and JNK Phosphorylation

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Ting Li ◽  
Fenggen Yan ◽  
Rui Wang ◽  
Hua Zhou ◽  
Liang Liu
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Cell Activation ◽  
Nuclear Translocation ◽  
Lymphocyte Activation ◽  
Immunosuppressive Agent ◽  
Buffy Coat ◽  
T Lymphocyte Activation

The key role of T cells has been elaborated in mediating immune responses and pathogenesis of human inflammatory and autoimmune conditions. In the current study the effect of shikonin, a compound isolated from a medicinal plant, on inhibition of T-cell activation was firstly examined by using primary human T lymphocytes isolated from buffy coat. Results showed that shikonin dose dependently suppressed T-cell proliferation, IL-2 and IFN-γsecretion, CD69 and CD25 expression, as well as cell cycle arrest activated by costimulation of PMA/ionomycin or OKT-3/CD28 monoclonal antibodies. Moreover, these inhibitory responses mediated by shikonin were found to be associated with suppression of the NF-κB signaling pathway via inhibition of the IKKα/βphosphorylation, IκB-αphosphorylation and degradation, and NF-κB nuclear translocation by directly decreasing IKKβactivity. Moreover, shikonin suppressed JNK phosphorylation in the MAPKs pathway of T cells. In this connection, we conclude that shikonin could suppress T lymphocyte activation through suppressing IKKβactivity and JNK signaling, which suggests that shikonin is valuable for further investigation as a potential immunosuppressive agent.

scholarly journals Immune cell populations in cutaneous delayed-type hypersensitivity.

1983 ◽  
Vol 158 (4) ◽  
pp. 1227-1242 ◽  
Author(s):  
J L Platt ◽  
B W Grant ◽  
A A Eddy ◽  
A F Michael
Keyword(s):  
Monoclonal Antibodies ◽  
T Lymphocytes ◽  
T Lymphocyte ◽  
Mononuclear Cells ◽  
Lymphocyte Activation ◽  
Delayed Type Hypersensitivity ◽  
Cell Populations ◽  
T Lymphocyte Activation ◽  
Cutaneous Response ◽  
Leu 7

Delayed-type hypersensitivity (DTH) is a prototypic T lymphocyte-mediated response to antigenic challenge. In this study, mononuclear cells infiltrating the skin during cutaneous response to tuberculin in presensitized human subjects (responders) and nonimmune controls were identified using monoclonal antibodies by indirect immunofluorescence. In both responders and controls the infiltrate consisted mainly of T lymphocytes (T11+ and OKT3+) and monocytes (OKM1+, 63D3+, Mo2+) which initially accumulated in proximity to small blood vessels and later infiltrated the interstitial dermis and epidermis. More T lymphocytes reacted with OKT4 than with OKT8. 6 h after tuberculin the ratio of OKT4/OKT8 in tissue from responders exceeded that in blood, whereas in tissues studied at 15-48 h and in all control tissues those ratios in blood and tissue were similar. Evidence of T lymphocyte activation was sought using monoclonal antibodies anti-Tac, OKT9, and OKT10. In responders but not in controls the proportion of infiltrating cells reactive with these antibodies increased during the course of DTH. The presence of activated T lymphocytes in tissue was not associated with a comparable increase in peripheral blood cell populations identified by anti-Tac and OKT10. Studies using anti-B1, Leu-7, and anti-IgD/IgM revealed comparatively few reactive cells. Dual-labeling studies demonstrated that most Leu-7--reactive cells also bound T11 while fewer bound OKM1 or OKT8 and that cells reactive with OKIa1 and T11 constituted largely nonoverlapping populations. Specific patterns of reactivity were not observed when tissues were stained with anti-human C3, or poly C9-MA, a monoclonal antibody reactive with a neoantigen on polymerized C9 of the membrane attack complex of complement. The number of epidermal Langerhans cells identified by OKT6 was similar in responders and controls. Thus, the cutaneous response to tuberculin in sensitized individuals is characterized by early enrichment of the OKT4 subpopulation of T lymphocytes in tissue infiltrates and subsequent (15-48 h) evidence of T lymphocyte activation.

scholarly journals Hydrogen peroxide promotes the activation of preeclampsia peripheral T cells

2018 ◽  
Vol 24 (4) ◽  
pp. 203-209 ◽  
Author(s):  
Jingzhu Lv ◽  
Xiaojie Zhang ◽  
Caizhi Wang ◽  
Hongtao Wang ◽  
Ting Wang ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Immune Activation ◽  
Lymphocyte Activation ◽  
Neutrophil Granulocytes ◽  
T Lymphocyte Activation ◽  
Hla Dr ◽  
Intracellular Ros ◽  
Oxidative Stress Status ◽  
High Oxidative Stress

Preeclampsia (PE) is a pregnancy disorder with a high mortality rate. Patients with PE exhibit systemic high oxidative stress status and inflammatory immune activation. This study aims to define the role of H2O2 in the activation of neutrophils and T lymphocytes in PE patients. CD3+/HLA-DR+ cells in blood from PE patients are remarkably increased compared with those of normal non-pregnancies or normal pregnancies, while the percentage of CD3+/CD62L+ cells is significantly reduced in PE patients compared to normal pregnancies. Furthermore, CD62L levels in granulocytes of periphery blood of PE patients are significantly higher than non-pregnancies, but significantly lower than normal pregnancies. To characterize the effects of intracellular reactive oxygen species (ROS) on T lymphocyte activation in PE patients, PBMCs from normal pregnancies were challenged with H2O2, and intracellular ROS levels in neutrophil granulocytes, as well as T cell surface marker levels, have been determined. We confirm that H2O2 exposure increases intracellular ROS levels in neutrophil granulocytes, and increases the proportion of CD3+/HLA-DR+ cells, but does not alter the percentage of CD3+/CD62L+ cells in PBMCs. Our study has confirmed dysregulated CD3+/HLA-DR+ and CD3+/CD62L+ T lymphocytes in PE patient peripheral blood, and the dysregulative effects of H2O2 on T lymphocyte activation, suggesting a novel mechanism of immune activation in PE.

scholarly journals Causes of T lymphocyte activation in HIV-infected patients coinfected with hepatitis C virus

2016 ◽  
Vol 88 (11) ◽  
pp. 22-28
Author(s):  
K V Shmagel ◽  
N G Shmagel ◽  
L B Korolevskaya ◽  
E V Saydakova ◽  
V A Chereshnev
Keyword(s):  
T Cells ◽  
Hepatitis C ◽  
T Cell ◽  
T Lymphocytes ◽  
T Cell Activation ◽  
T Lymphocyte ◽  
Cell Activation ◽  
Lymphocyte Activation ◽  
Cd8 T Cell ◽  
Cd8 T Lymphocytes

Aim. To establish the causes of T lymphocyte activation in human immunodeficiency virus (HIV)-infected patients coinfected with hepatitis C (HCV) who are adherent to their antiretroviral therapy regimen and interferon untreated. Subjects and methods. Examinations were made in 62 people who were HIV+HCV-positive (n=21), HIV+HCV-negative (n=21), and noninfected volunteers (n=20). The activation (CD38+HLA-DR+) and proliferation (Ki-67+) of CD4+ and CD8+ T lymphocytes were estimated. The blood concentration of intestinal fatty acid-binding protein (I-FABP) was determined. Results. The proportion of activated cells among the CD4+ T lymphocytes was equal in the HIV+HCV-positive and HIV+HCV-negative groups. But these indicators were statistically significantly higher than those in the controls (HIV- HCV-). CD8+ T cell activation was greater in the HIV/HCV-coinfected patients than that in the other groups and that was higher in the HIV monoinfected than in the noninfected. The blood I-FABP concentrations were elevated in the HIV+HCV-positive and HIV+HCV groups compared with those in the HIV-HCV-negative group, but these did not differ among themselves. In the HIV+HCV-negative patients, CD4+ and CD8+ T cell activation directly and statistically significantly correlated with blood I-FABP levels. In the HIV+HCV-positive group, this correlation remained only for CD4+ T lymphocytes. CD8+ T cell activation in HIV/HCV-coinfected patients was unrelated to I-FABP concentrations. Conclusion. The increased activation of CD4+ and CD8+ T lymphocytes in HIV monoinfection was found to be associated with intestinal epithelial destruction and unrelated to cell division processes. In HIV/HCV coinfection, the activated state of CD4+ T cells is determined by both the level of proliferative processes and impairment of the intestinal barrier and that of CD8+ T cells is only by proliferation.

scholarly journals Isolation and structural characterization of the human 4F2 heavy-chain gene, an inducible gene involved in T-lymphocyte activation.

1988 ◽  
Vol 8 (9) ◽  
pp. 3809-3819 ◽  
Author(s):  
K M Gottesdiener ◽  
B A Karpinski ◽  
T Lindsten ◽  
J L Strominger ◽  
N H Jones ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Surface ◽  
T Lymphocyte ◽  
Heavy Chain ◽  
Peripheral Blood ◽  
Interleukin 2 ◽  
Lymphocyte Activation ◽  
Upstream Region ◽  
Activated T Cells ◽  
T Lymphocyte Activation

The human 4F2 cell surface antigen is a 120-kilodalton (kDa) disulfide-linked heterodimer which is composed of an 80- to 90-kDa glycosylated heavy chain (4F2HC) and a 35- to 40-kDa nonglycosylated light chain (4F2LC). 4F2 belongs to a family of inducible cell surface molecules which are involved in T-lymphocyte activation and growth. To better understand the molecular mechanism(s) that controls 4F2HC gene expression in both resting and activated T cells, a 4F2HC human genomic clone was isolated and structurally characterized. The 4F2HC gene spans 8 kilobases of chromosome 11 and is composed of nine exons. The 5' upstream region of the gene displays several properties which are characteristic of housekeeping genes. It is G+C rich and hypomethylated in peripheral blood lymphocyte DNA and contains multiple binding sites for the Sp1 transcription factor while lacking TATA or CCAAT sequences. This region of the gene also displays sequence homologies with several other inducible T-cell genes, including the interleukin-2, interleukin-2 receptor alpha chain, dihydrofolate reductase, thymidine kinase, and transferrin receptor genes. A 255-base-pair fragment of the 4F2HC gene which contains 154 base pairs of the 5' flanking sequence was able to efficiently promote expression of the bacterial chloramphenicol acetyltransferase gene in human Jurkat T cells, indicating that it contains promoter or enhancer (or both) sequences. Analyses of chromatin structure in resting and lectin-activated T cells revealed the presence of stable DNase I-hypersensitive sites within both the 5' flanking and intron 1 regions of the 4F2HC gene. Although the 4F2HC gene displayed many of the structural features characteristic of a constitutively expressed gene, lectin-mediated activation of resting peripheral blood T lymphocytes resulted in a dramatic increase in steady-state levels of 4F2HC mRNA.

Effect of dexamethasone on expression of adhesion molecules on CD4+ lymphocytes

1996 ◽  
Vol 271 (1) ◽  
pp. L79-L84
Author(s):  
J. M. Hughes ◽  
W. A. Sewell ◽  
J. L. Black ◽  
C. L. Armour
Keyword(s):  
T Lymphocytes ◽  
Cell Surface ◽  
T Lymphocyte ◽  
Lymphocyte Activation ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Cell Surface Markers ◽  
T Lymphocyte Activation ◽  
Beta 1 Integrin ◽  
Memory T Lymphocytes

Despite the widespread use of corticosteroids in asthma therapy, little is known of the effects of corticosteroids on cell surface markers involved in T lymphocyte activation and adhesion. We used flow cytometry to analyze the effects of 1, 10, and 100 nM dexamethasone on expression of markers on resting and phytohemagglutinin (PHA)-stimulated peripheral blood CD4+ T lymphocytes. Expression of the leukocyte common antigen CD45 was significantly (P = 0.016, n = 3) increased from an average mean fluorescence intensity of 215.8 [95% confidence intervals (CI): 100.5, 463.5] on cells from unstimulated cultures to 334.2 (CI: 167.9, 663.7) on cells from PHA-stimulated cultures after 70-h incubation. At the same time, the percentage of cells also expressing the CD45RO isoform, a marker of memory T lymphocytes, increased significantly (P = 0.0006, n = 3) from 54.4 +/- 1.3% (unstimulated) to 92.8 +/- 0.6% (stimulated). Dexamethasone had no significant effect on expression of CD45 or CD45RO, including the observed changes. Dexamethasone also did not affect expression of the beta 1-integrin VLA-4. These results suggest that corticosteroids do not modulate the cell surface expression of these molecules involved in CD4+ T lymphocyte activation, adhesion, and recirculation.

scholarly journals Induction of Hyporesponsiveness and Impaired T Lymphocyte Activation by the CD31 Receptor:Ligand Pathway in T Cells

2001 ◽  
Vol 166 (4) ◽  
pp. 2364-2371 ◽  
Author(s):  
Elisabeth Prager ◽  
Günther Staffler ◽  
Otto Majdic ◽  
Marcus D. Säemann ◽  
Samuel Godár ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocyte ◽  
Lymphocyte Activation ◽  
T Lymphocyte Activation
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