scholarly journals Cellular Immune Responses to ESAT-6 Discriminate between Patients with Pulmonary Disease Due to Mycobacterium avium Complex and Those with Pulmonary Disease Due toMycobacterium tuberculosis

1999 ◽  
Vol 6 (4) ◽  
pp. 606-609 ◽  
Author(s):  
A. David Lein ◽  
C. Fordham von Reyn ◽  
Pernille Ravn ◽  
C. Robert Horsburgh ◽  
Lorraine N. Alexander ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Pulmonary Disease ◽  
Mycobacterium Avium ◽  
Mononuclear Cells ◽  
Negative Control ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ ◽  
Cellular Immune

ABSTRACT ESAT-6 (for 6-kDa early secreted antigenic target) is a secreted antigen found almost exclusively in organisms of theMycobacterium tuberculosis complex. We compared in vitro gamma interferon (IFN-γ) responses by peripheral blood mononuclear cells to this antigen in patients with pulmonary disease due to eitherMycobacterium avium complex (MAC) or Mycobacterium tuberculosis with those in healthy, skin test-negative, control subjects. Significant IFN-γ responses to ESAT-6 were detected in 16 (59%) of 27 M. tuberculosis pulmonary disease patients, 0 (0%) of 8 MAC disease patients, and 0 (0%) of 8 controls. Significant IFN-γ responses to M. tuberculosis purified protein derivative were detected in 23 (85%) of 27 M. tuberculosisdisease patients, 2 (25%) of 8 MAC disease patients, and 5 (63%) of 8 healthy controls. M. avium sensitin was recognized in 24 (89%) of 27 M. tuberculosis disease patients, 4 (50%) of 8 MAC disease patients, and 1 (13%) of 8 controls. IFN-γ responses to ESAT-6 are specific for disease due toM. tuberculosis and are not observed in patients with MAC disease or in healthy controls.

scholarly journals Cholera Caused by Vibrio cholerae O1 Induces T-Cell Responses in the Circulation

2009 ◽  
Vol 77 (5) ◽  
pp. 1888-1893 ◽  
Author(s):  
Taufiqur Rahman Bhuiyan ◽  
Samuel B. Lundin ◽  
Ashraful Islam Khan ◽  
Anna Lundgren ◽  
Jason B. Harris ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Vibrio Cholerae ◽  
Mononuclear Cells ◽  
Acute Stage ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Vibrio Cholerae O1 ◽  
Ifn Γ ◽  
Cellular Immune

ABSTRACT Considerable effort is being made to understand the acute and memory antibody responses in natural cholera infection, while rather less is known about the roles of cellular immune responses involving T and B lymphocytes. We studied responses in adult patients hospitalized with cholera caused by Vibrio cholerae O1. Peripheral blood mononuclear cells from patients (n = 15) were analyzed by flow cytometry after stimulation with V. cholerae O1 membrane protein (MP) or toxin-coregulated pilus antigen (TcpA). The gamma interferon (IFN-γ) and interleukin-13 (IL-13) responses in stimulated-lymphocyte supernatants were studied. The responses were compared with those of healthy controls (n = 10). Patients responded with increased frequencies of gut-homing CD4+ T cells (CD4+ β7+), gut-homing CD8+ T cells (CD8+ β7+), and gut-homing B cells (CD19+ β7+) at the early and/or late convalescent stages compared to the acute stage. After stimulation with MP or TcpA, proliferation of CD4+ and CD8+ T cells was increased at the acute stage and/or early convalescent stage compared to healthy controls. Increased IL-13 and IFN-γ responses were observed after antigenic stimulation at the acute and convalescent stages compared to healthy controls. Thus, increases in the levels of gut-homing T and B cells, as well as involvement of CD8 and CD4 Th1-mediated (IFN-γ) and CD4 Th2-mediated (IL-13) cytokine responses, take place in acute dehydrating disease caused by V. cholerae O1. Further studies are needed to determine if such responses are also stimulated after immunization with oral cholera vaccines and if these responses play a role in protection following exposure to cholera.

scholarly journals Defective Regulatory B Cells Are Associated With Thyroid-Associated Ophthalmopathy

2019 ◽  
Vol 104 (9) ◽  
pp. 4067-4077 ◽  
Author(s):  
Guo Chen ◽  
Yungang Ding ◽  
Qian Li ◽  
Yanbing Li ◽  
Xiaofeng Wen ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Regulatory B Cells ◽  
Peripheral Blood Mononuclear ◽  
Thyroid Associated Ophthalmopathy ◽  
Ifn Γ

Abstract Purpose To investigate the change in IL-10–producing regulatory B cells (Breg), which suppress peripheral immune responses, in patients with thyroid-associated ophthalmopathy (TAO). Methods Peripheral blood mononuclear cells (PBMCs) were isolated from healthy controls (n = 54), patients with Graves disease (n = 26), and patients with TAO (N=125), and stimulated with CpG/CD40L. The frequency of IL-10–producing Bregs and the expression of IL-10 in response to TSH stimulation were measured by flow cytometry. CD4+ T cells were cultured with Breg-depleted PBMCs to elucidate the function of Bregs in patients with TAO. The potential immunoregulatory mechanism was also investigated by Western blot and chromatin immunoprecipitation assays. Results Patients with active TAO had higher baseline levels of Bregs in their peripheral blood than both healthy controls and inactive patients. TSH promoted Bregs. Bregs from patients with TAO were defective in suppressing the activation of interferon (IFN)-γ+ and IL-17+ T cells in vitro. Conclusions Regulatory B cells in patients with TAO are functionally defective, suggesting that the defective Bregs might be responsible for the pathogenesis of TAO.

scholarly journals Neutralization of Interleukin-10 Significantly Enhances Gamma Interferon Expression in Peripheral Blood by Stimulation with Johnin Purified Protein Derivative and by Infection with Mycobacterium avium subsp. paratuberculosis in Experimentally Infected Cattle with Paratuberculosis

2004 ◽  
Vol 72 (4) ◽  
pp. 2425-2428 ◽  
Author(s):  
Joram J. Buza ◽  
Hirokazu Hikono ◽  
Yasuyuki Mori ◽  
Reiko Nagata ◽  
Sachiyo Hirayama ◽  
...  
Keyword(s):  
Mycobacterium Avium ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Interleukin 10 ◽  
Suppressive Effect ◽  
Gamma Interferon ◽  
Peripheral Blood Mononuclear ◽  
Purified Protein Derivative ◽  
Ifn Γ

ABSTRACT Monoclonal antibody neutralization of interleukin-10 (IL-10) increased Johnin purified protein derivative-induced whole-blood gamma interferon (IFN-γ) secretion 23-fold and also increased IFN-γ secretion ninefold following in vitro Mycobacterium avium subsp. paratuberculosis infection of peripheral blood mononuclear cells. These results demonstrate the suppressive effect of IL-10 on immune responses to M. avium subsp. paratuberculosis infection in cattle.

scholarly journals Modulation of Gamma Interferon Receptor 1 by Mycobacterium tuberculosis: a Potential Immune Response Evasive Mechanism

2007 ◽  
Vol 75 (5) ◽  
pp. 2500-2510 ◽  
Author(s):  
Amit Singhal ◽  
Anand Jaiswal ◽  
Virendra K. Arora ◽  
Hanumanthappa K. Prasad
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Surface Expression ◽  
Gamma Interferon ◽  
Mobility Shift ◽  
Down Regulation ◽  
Peripheral Blood Mononuclear ◽  
Ifn Γ

ABSTRACT Mycobacterium tuberculosis inhibits gamma interferon (IFN-γ)-mediated antimycobacterial action by adopting diverse mechanisms. IFN-γ binds to its receptor, IFN-γR, in order to initiate proper signaling. We have observed reduced surface expression levels of IFN-γ receptor 1 (IFN-γR1) in untreated pulmonary tuberculosis patients compared to those in healthy individuals (P < 0.01). Following antitubercular therapy, the expression of IFN-γR1 was restored in these patients. To delineate the mechanism by which M. tuberculosis modulates IFN-γR1, in vitro experiments were designed, wherein the down modulation of IFN-γR1 surface expression was observed for CD14+ cells in peripheral blood mononuclear cells (PBMCs) cocultured with live M. tuberculosis compared to that for uninfected cells (P < 0.01). No modulation of IFN-γR1 expression was observed for CD14+ cells in PBMCs infected with Mycobacterium smegmatis. A time-dependent decrease in IFN-γR1 mRNA expression was observed for PBMCs infected with M. tuberculosis. Similar down modulation of IFN-γR1 protein and mRNA expression in phorbol myristate acetate-differentiated THP-1 cells (pdTHP-1) by M. tuberculosis was observed (P < 0.01). Using reporter gene analysis of 5′ deletion constructs of the IFN-γR1 gene (IFNGR1) promoter, the decrease in IFN-γR1 mRNA in M. tuberculosis-infected pdTHP-1 cells was shown to be due to the decreased transcription of IFNGR1. By immunoblotting and electrophoretic mobility shift assays, the down regulation of stimulating protein 1 (Sp1) expression and its recruitment on the phorbol ester-responsive element of the IFNGR1 promoter in M. tuberculosis-infected pdTHP-1 cells was observed. This down regulation of Sp1 in pdTHP-1 cells cocultured with M. tuberculosis may be responsible for the down regulation of IFN-γR1 expression, thereby potentially altering its receptivity to IFN-γ.

scholarly journals Characterization of Human Cellular Immune Responses to Novel Mycobacterium tuberculosis Antigens Encoded by Genomic Regions Absent in Mycobacterium bovis BCG

2008 ◽  
Vol 76 (9) ◽  
pp. 4190-4198 ◽  
Author(s):  
R. Al-Attiyah ◽  
A. S. Mustafa
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Mycobacterium Bovis ◽  
Healthy Subjects ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Cellular Immune Responses ◽  
Ifn Γ ◽  
Cellular Immune

ABSTRACT Comparative genomics has identified several regions of differences (RDs) between the infectious Mycobacterium tuberculosis and the vaccine strains of Mycobacterium bovis BCG. We aimed to evaluate the cellular immune responses induced by antigens encoded by genes predicted in 11 RDs. Synthetic peptides covering the sequences of RD1, RD4 to RD7, RD9 to RD13, and RD15 were tested for antigen-induced proliferation and secretion of Th1 cytokine, gamma interferon (IFN-γ), by peripheral blood mononuclear cells (PBMC) obtained from culture-proven pulmonary tuberculosis (TB) patients and M. bovis BCG-vaccinated healthy subjects. Among the peptide pools, RD1 induced the best responses in both donor groups and in both assays. In addition, testing of TB patients' PBMC for secretion of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin 6 [IL-6], IL-8, and IL-1β), Th1 cytokines (IFN-γ, IL-2, and TNF-β), and Th2 cytokines (IL-4, IL-5, and IL-10) showed differential effects of RD peptides in the secretion of IFN-γ and IL-10, with high IFN-γ/IL-10 ratios (32 to 5.0) in response to RD1, RD5, RD7, RD9, and RD10 and low IFN-γ/IL-10 ratios (<1.0) in response to RD12, RD13, and RD15. Peptide-mixing experiments with PBMC from healthy subjects showed that secretion of large quantities of IL-10 in response to RD12 and RD13 correlated with inhibition of Th1 responses induced by RD1 peptides. In conclusion, our results suggest that M. tuberculosis RDs can be divided into two major groups—one group that activates PBMC to preferentially secrete IFN-γ and another group that activates preferential secretion of IL-10—and that these two groups of RDs may have roles in protection against and pathogenesis of TB, respectively.

scholarly journals The role of CXCR3 and its ligands expression in Brucellar spondylitis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Xin Hu ◽  
Xiaoqian Shang ◽  
Liang Wang ◽  
Jiahui Fan ◽  
Yue Wang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Inflammatory Infiltration ◽  
Peripheral Blood Mononuclear ◽  
Expression Levels ◽  
Inflammatory Damage ◽  
Ifn Γ ◽  
Mrna Expression Levels

Abstract Aim Brucellar spondylitis (BS) is one of the most serious complications of brucellosis. CXCR3 is closely related to the severity of disease infection. This research aimed to study the degree of BS inflammatory damage through analyzing the expression levels of CXCR3 and its ligands (CXCL9 and CXCL10) in patients with BS. Methods A total of 29 BS patients and 15 healthy controls were enrolled. Real-Time PCR was used to detect the mRNA expression levels of IFN-γ, CXCR3, CXCL9 and CXCL10 in peripheral blood mononuclear cells (PBMCs) of BS patients and healthy controls. Hematoxylin-Eosin staining was used to show the pathological changes in BS lesion tissues. Immunohistochemistry staining was used to show the protein expression levels of Brucella-Ab, IFN-γ, CXCR3, CXCL9 and CXCL10 in BS lesion tissues. At the same time, ELISA was used to detect the serum levels of IFN-γ, CXCL9 CXCL10 and autoantibodies against CXCR3 in patients with BS. Results In lesion tissue of BS patients, it showed necrosis of cartilage, acute or chronic inflammatory infiltration. Brucella-Ab protein was abundantly expressed in close lesion tissue. And the protein expression levels of IFN-γ, CXCR3 and CXCL10 were highly expressed in close lesion tissue and serum of BS patients. At the same time, the mRNA expression levels of IFN-γ, CXCR3 and CXCL10 in PBMCs of BS patients were significantly higher than those in controls. Conclusion In our research, the expression levels of IFN-γ, CXCR3 and its ligands were significantly higher than those in controls. It suggested that high expression levels of IFN-γ, CXCR3 and its ligands indicated a serious inflammatory damage in patients with BS.

scholarly journals Protection of BALB/c Mice against Brucella abortus 544 Challenge by Vaccination with Bacterioferritin or P39 Recombinant Proteins with CpG Oligodeoxynucleotides as Adjuvant

2001 ◽  
Vol 69 (8) ◽  
pp. 4816-4822 ◽  
Author(s):  
Ayman Al-Mariri ◽  
Anne Tibor ◽  
Pascal Mertens ◽  
Xavier De Bolle ◽  
Patrick Michel ◽  
...  
Keyword(s):  
Recombinant Proteins ◽  
Brucella Abortus ◽  
Mononuclear Cells ◽  
Brucella Melitensis ◽  
Cpg Odn ◽  
Peripheral Blood Mononuclear ◽  
Recombinant Antigens ◽  
Cpg Oligodeoxynucleotides ◽  
Ifn Γ

ABSTRACT The P39 and the bacterioferrin (BFR) antigens of Brucella melitensis 16M were previously identified as T dominant antigens able to induce both delayed-type hypersensivity in sensitized guinea pigs and in vitro gamma interferon (IFN-γ) production by peripheral blood mononuclear cells from infected cattle. Here, we analyzed the potential for these antigens to function as a subunitary vaccine against Brucella abortus infection in BALB/c mice, and we characterized the humoral and cellular immune responses induced. Mice were injected with each of the recombinant proteins alone or adjuvanted with either CpG oligodeoxynucleotides (CpG ODN) or non-CpG ODN. Mice immunized with the recombinant antigens with CpG ODN were the only group demonstrating both significant IFN-γ production and T-cell proliferation in response to either Brucella extract or to the respective antigen. The same conclusion holds true for the antibody response, which was only demonstrated in mice immunized with recombinant antigens mixed with CpG ODN. The antibody titers (both immunoglobulin G1 [IgG1] and IgG2a) induced by P39 immunization were higher than the titers induced by BFR (only IgG2a). Using a B. abortus 544 challenge, the level of protection was analyzed and compared to the protection conferred by one immunization with the vaccine strain B19. Immunization with P39 and CpG ODN gave a level of protection comparable to the one conferred by B19 at 4 weeks postchallenge, and the mice were still significantly protected at 8 weeks postchallenge, although to a lesser extent than the B19-vaccinated group. Intriguingly, no protection was detected after BFR vaccination. All other groups did not demonstrate any protection.

scholarly journals The Anthrax Vaccine Adsorbed Vaccine Generates Protective Antigen (PA)-Specific CD4+ T Cells with a Phenotype Distinct from That of Naïve PA T Cells

2008 ◽  
Vol 76 (10) ◽  
pp. 4538-4545 ◽  
Author(s):  
William W. Kwok ◽  
Junbao Yang ◽  
Eddie James ◽  
John Bui ◽  
Laurie Huston ◽  
...  
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Protective Antigen ◽  
Ex Vivo ◽  
Cytokine Profile ◽  
T Cell Epitopes ◽  
Peripheral Blood Mononuclear ◽  
Anthrax Vaccine ◽  
Cellular Immune

ABSTRACT Cellular immune responses against protective antigen (PA) of Bacillus anthracis in subjects that received the anthrax vaccine adsorbed (AVA) vaccine were examined. Multiple CD4+ T-cell epitopes within PA were identified by using tetramer-guided epitope mapping. PA-reactive CD4+ T cells with a CD45RA− phenotype were also detected by direct ex vivo staining of peripheral blood mononuclear cells (PBMC) with PA-specific tetramers. Surprisingly, PA-specific T cells were also detected in PBMC of nonvaccinees after a single cycle of in vitro PA stimulation. However, PA-reactive CD4+ T cells in nonvaccinees occurred at lower frequencies than those in vaccinees. The majority of PA-reactive T cells from nonvaccinees were CD45RA+ and exhibited a Th0/Th1 cytokine profile. In contrast, phenotyping and cytokine profile analyses of PA-reactive CD4+ T cells from vaccinees indicated that vaccination leads to commitment of PA-reactive T cells to a Th2 lineage, including generation of PA-specific, pre-Th2 central memory T cells. These results demonstrate that the current AVA vaccine is effective in skewing the development of PA CD4+ T cells to the Th2 lineage. The data also demonstrated the feasibility of using class II tetramers to analyze CD4+ cell responses and lineage development after vaccination.

scholarly journals Evaluation of Immunostimulatory Activities of Synthetic Mannose-Containing Structures Mimicking the β-(1→2)-Linked Cell Wall Mannans of Candida albicans

2012 ◽  
Vol 19 (11) ◽  
pp. 1889-1893 ◽  
Author(s):  
Kaarina Ranta ◽  
Kaisa Nieminen ◽  
Filip S. Ekholm ◽  
Moniká Poláková ◽  
Mattias U. Roslund ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Peripheral Blood Mononuclear ◽  
Content Type ◽  
Mouse Macrophages ◽  
Ifn Γ ◽  
Low Levels ◽  
Necrosis Factor

ABSTRACTImmunostimulatory properties of synthetic structures mimicking the β-(1→2)-linked mannans ofCandida albicanswere evaluatedin vitro. Contrary to earlier observations, tumor necrosis factor (TNF) production was not detected after stimulation with mannotetraose in mouse macrophages. Divalent disaccharide 1,4-bis(α-d-mannopyranosyloxy)butane induced TNF and some molecules induced low levels of gamma interferon (IFN-γ) in human peripheral blood mononuclear cells (PBMC).

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