scholarly journals Exogenous Control of the Expression of Group I CD1 Molecules Competent for Presentation of Microbial Nonpeptide Antigens to Human T Lymphocytes

2011 ◽  
Vol 2011 ◽  
pp. 1-27 ◽  
Author(s):  
Angelo Aquino ◽  
Grazia Graziani ◽  
Ornella Franzese ◽  
Salvatore P. Prete ◽  
Enzo Bonmassar ◽  
...  

Group I CD1 (CD1a, CD1b, and CD1c) glycoproteins expressed on immature and mature dendritic cells present nonpeptide antigens (i.e., lipid or glycolipid molecules mainly of microbial origin) to T cells. Cytotoxic CD1-restricted T lymphocytes recognizing mycobacterial lipid antigens were found in tuberculosis patients. However, thanks to a complex interplay betweenmycobacteriaand CD1 system,M. tuberculosispossesses a successful tactic based, at least in part, on CD1 downregulation to evade CD1-dependent immunity. On the ground of these findings, it is reasonable to hypothesize that modulation of CD1 protein expression by chemical, biological, or infectious agents could influence host's immune reactivity againstM. tuberculosis-associated lipids, possibly affecting antitubercular resistance. This scenario prompted us to perform a detailed analysis of the literature concerning the effect of external agents on Group I CD1 expression in order to obtain valuable information on the possible strategies to be adopted for driving properly CD1-dependent immune functions in human pathology and in particular, in human tuberculosis.

PEDIATRICS ◽  
1995 ◽  
Vol 96 (1) ◽  
pp. 77-77
Author(s):  
H Ozkan ◽  
N Olgun ◽  
E Sasmaz

This study was a case-control study of 44 children ages 3 to 24 months. The purpose of the study was to compare the humoral and cellular immunity of 29 patients (Group I) who were less than the 3rd percentile for weight by Turkish standards versus a control group of 15 patients (Group II) with weights between the 25th and 90th percentiles. The Group I patients were considered to have protein energy malnutrition (PEM) with various degrees of severity based on a Turkish classification method established by Dogramaci and Wray in 1958. None of the Group I patients had frank kwashiorkor, but 19 had bronchopneumonia, six had gastroenteritis, and four had both forms of infection at the time studies were done. Detailed immunologic evaluation was carried out on all the subjects including IgG, IgM, IgA, C3, mature T lymphocytes (CD3+), helper/inducer T Lymphocytes (CD4+) and suppressor/cytotoxic T lymphocytes (CD8+). The authors chose to study patients with PEM and infections because the immune response is more likely to be suppressed at this time. In the PEM group all of the immunoglobulins (IgG, IgM, IgA) were significantly elevated over the controls level (P < .01). This hyperimmunoglobulinemia state has been previously reported and could be secondary to reduced suppressor T lymphocytes (C8+). C3 complement levels were also significantly lower (P < .01) than controls, which have been previously noted. These low C3 levels could be secondary to decreased production from the liver or increased utilization with an intercurrent infection. In evaluating the lymphocyte series CD3+, CD4+, and CD8+ were all significantly reduced while CD4/CD8 levels were normal.


2006 ◽  
Vol 148 (6) ◽  
pp. 760-768 ◽  
Author(s):  
Annalisa Chiocchetti ◽  
Gianluca Miglio ◽  
Riccardo Mesturini ◽  
Federica Varsaldi ◽  
Marco Mocellin ◽  
...  

2019 ◽  
Vol 11 (10) ◽  
pp. 384-393 ◽  
Author(s):  
Sarah Hyun Ji Kim ◽  
Daniel A Hammer

Abstract In order to perform critical immune functions at sites of inflammation, circulatory T lymphocytes must be able to arrest, adhere, migrate and transmigrate on the endothelial surface. This progression of steps is coordinated by cellular adhesion molecules (CAMs), chemokines, and selectins presented on the endothelium. Two important interactions are between Lymphocyte Function-associated Antigen-1 (LFA-1) and Intracellular Adhesion Molecule-1 (ICAM-1) and also between Very Late Antigen-4 (VLA-4) and Vascular Cell Adhesion Molecule-1 (VCAM-1). Recent studies have shown that T lymphocytes and other cell types can migrate upstream (against the direction) of flow through the binding of LFA-1 to ICAM-1. Since upstream migration of T cells depends on a specific adhesive pathway, we hypothesized that mechanotransduction is critical to migration, and that signals might allow T-cells to remember their direction of migration after the flow is terminated. Cells on ICAM-1 surfaces migrate against the shear flow, but the upstream migration reverts to random migration after the flow is stopped. Cells on VCAM-1 migrate with the direction of flow. However, on surfaces that combine ICAM-1 and VCAM-1, cells crawl upstream at a shear rate of 800 s−1 and continue migrating in the upstream direction for at least 30 minutes after the flow is terminated—we call this ‘migrational memory’. Post-flow upstream migration on VCAM-1/ICAM-1 surfaces is reversed upon the inhibition of PI3K, but conserved with cdc42 and Arp2/3 inhibitors. Using an antibody against VLA-4, we can block migrational memory on VCAM-1/ICAM-1 surfaces. Using a soluble ligand for VLA-4 (sVCAM-1), we can promote migrational memory on ICAM-1 surfaces. These results indicate that, while upstream migration under flow requires LFA-1 binding to immobilized ICAM-1, signaling from VLA-4 and PI3K activity is required for the migrational memory of CD4+ T cells. These results indicate that crosstalk between integrins potentiates the signal of upstream migration.


2018 ◽  
Author(s):  
Egle Cekanaviciute ◽  
Anne-Katrin Pröbstel ◽  
Anna Thomann ◽  
Tessel F. Runia ◽  
Patrizia Casaccia ◽  
...  

AbstractMultiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by adaptive and innate immune system dysregulation. Recent work has revealed moderate alteration of gut microbial communities in subjects with MS and in experimental, induced models. However, a mechanistic understanding linking the observed changes in the microbiota and the presence of the disease is still missing. Chloroform-resistant, spore-forming bacteria have been shown to exhibit immunomodulatory properties in vitro and in vivo, but they have not yet been characterized in the context of human disease. This study addresses the community composition and immune function of this bacterial fraction in MS. We identify MS-associated spore-forming taxa and show that their presence correlates with impaired differentiation of IL-10 secreting, regulatory T lymphocytes in-vitro. Colonization of antibiotic-treated mice with spore-forming bacteria allowed us to identify some bacterial taxa favoring IL-10+ lymphocyte differentiation and others inducing differentiation of pro-inflammatory, IFNγ+ T lymphocytes. However, when fed into antibiotic-treated mice, both MS and control derived spore-forming bacteria were able to induce immunoregulatory responses.Our analysis also identified Akkermansia muciniphila as a key organism that may interact either directly or indirectly with spore-forming bacteria to exacerbate the inflammatory effects of MS-associated gut microbiota. Thus, changes in the spore-forming fraction may influence T lymphocyte-mediated inflammation in MS. This experimental approach of isolating a subset of microbiota based on its functional characteristics may be useful to investigate other microbial fractions at greater depth.ImportanceDespite the rapid emergence of microbiome related studies in human diseases, few go beyond a simple description of relative taxa levels in a select group of patients. Our study integrates computational analysis with in vitro and in vivo exploration of inflammatory properties of both complete microbial communities and individual taxa, revealing novel functional associations. We specifically show that while small differences exist between the microbiomes of MS patients and healthy subjects, these differences are exacerbated in the chloroform resistant fraction. We further demonstrate that, when purified from MS patients, this fraction is associated with impaired immunomodulatory responses in vitro.


Blood ◽  
1987 ◽  
Vol 69 (2) ◽  
pp. 369-380 ◽  
Author(s):  
LG Lum

Human marrow transplantation for the treatment of malignant and nonmalignant disorders is becoming an established modality of therapy. As in any aggressive therapeutic modality, the benefits must be balanced with the risks of the therapy. The aggressive chemoradiotherapy used to prepare patients for marrow transplantation creates a transient immunodeficiency disorder postgrafting until the transferred donor marrow reestablishes a competent immune system. Immune reconstitution posttransplant follows a general pattern developing from immature to mature immune functions. Immune reactivity during the first month postgrafting is extremely low. Cytotoxic and phagocytic functions recover by day 100, while more specialized and cooperative functions of T and B cells remain impaired up to one year or more postgrafting. After the first year postgrafting, the various components of the immune systems of most healthy marrow recipients begin to work synchronously, whereas the immune systems of recipients with chronic graft-v-host disease (GVHD) remain crippled. Recent evidence shows that transfer of specific immunity from marrow donors to marrow recipients plays a role in reestablishing immunocompetence. Transferred antigen-specific immunity may explain why more recipients do not die from overwhelming infections.


2019 ◽  
Vol 36 (2) ◽  
pp. 51-59
Author(s):  
N. I. Gulyaeva ◽  
G. G. Freind ◽  
N. G. Shmagel ◽  
L. B. Korolevskaya ◽  
E. V. Saidakova ◽  
...  

Aim. To assess the morphological changes in inguinal lymph nodes among patients with stage 4a HIV infection, who receive antiretroviral therapy. Materials and methods. There were examined 12 HIV-infected patients with stage 4a, treated at “Perm Regional Center for Prevention and Fight against AIDS and Infectious Diseases”, who received antiretroviral therapy for 2 years. Two groups of patients were formed: group I – 6 persons, whose CD+ blood lymphocyte number was more than 350 in 1 mcl; group II – 6 persons with CD+ blood lymphocyte number less than 350 in 1 mcl. Inguinal lymph nodes (ILN) were taken under local anesthesia, histological preparations were prepared by traditional scheme, stained with hematoxylin and eosin using Masson three-colour staining. In immunohistochemical reactions expression of Ki-67 and CD+ markers was estimated. Results.Histoarchitectonics of lymph nodes was changed as a result of massive development of sclerosis in the region of hilum, capsule and trabecules. Against the background of sclerosis, there occurred lymphocyte depletion, change in structure of stromal cells and neoangiogenesis in all the zones of the lymph node. In the regions of sclerosis, death of lymphocytes was revealed. In patients of the second group, more active development of follicles with the centers of reproduction in the lymph node cortical substance, as well as growth of the number of Ki-67 maker-expressing cells was established Conclusions.In the inguinal lymph nodes, the development of sclerotic processes causes the death of T-lymphocytes, which, in their turn, are the source of lymphotoxin-β formation. Loss of CD+-T-lymphocytes is accompanied by deficit of lymphotoxin-β and induces the loss of fibroblastic reticular cells themselves, which through the production of IL-7 support the vital activity of T-cells.


Blood ◽  
1987 ◽  
Vol 69 (2) ◽  
pp. 369-380 ◽  
Author(s):  
LG Lum

Abstract Human marrow transplantation for the treatment of malignant and nonmalignant disorders is becoming an established modality of therapy. As in any aggressive therapeutic modality, the benefits must be balanced with the risks of the therapy. The aggressive chemoradiotherapy used to prepare patients for marrow transplantation creates a transient immunodeficiency disorder postgrafting until the transferred donor marrow reestablishes a competent immune system. Immune reconstitution posttransplant follows a general pattern developing from immature to mature immune functions. Immune reactivity during the first month postgrafting is extremely low. Cytotoxic and phagocytic functions recover by day 100, while more specialized and cooperative functions of T and B cells remain impaired up to one year or more postgrafting. After the first year postgrafting, the various components of the immune systems of most healthy marrow recipients begin to work synchronously, whereas the immune systems of recipients with chronic graft-v-host disease (GVHD) remain crippled. Recent evidence shows that transfer of specific immunity from marrow donors to marrow recipients plays a role in reestablishing immunocompetence. Transferred antigen-specific immunity may explain why more recipients do not die from overwhelming infections.


1975 ◽  
Vol 142 (5) ◽  
pp. 1231-1240 ◽  
Author(s):  
H Binz ◽  
H Wigzell

Anti-idiotypic antibodies made against antigen-binding receptors on T lymphocytes with specificity for certain Ag-B locus antigens selectively react with T lymphocytes with potential immune reactivity against the very same Ag-B antigens. This was shown by affinity chromatography of normal Lewis T lymphocytes on anti-Ig columns after contact with the relevant anti-idiotypic antiserum. Here, it could be shown that incubation of the cells with an anti-(Lewis-anti-BN) antiserum caused subsequent selective retention of potential graft-vs.-host (GvH)-reactive cells against BN on the anti-Ig column, whereas Lewis T cells with reactivity against DA or August (Au) (carrying distinct Ag-B antigens in comparison to BN) passed through. The retained cells could be eluted and shown to display highly increased reactivity against BN with virtually no reactivity left against DA or Au antigens. Analogous results were obtained using an anti-(Lewis-anti-DA) antiserum. The anti-idiotypic antibodies can be used in fluorescent antibody tests to directly visualize the idiotype-positive cells. Using the separation design described above we analyzed selectively enriched or deleted T lymphocytes for presence of idiotypic cells as well as specific GvH reactivity. A highly significant positive correlation was found between percentage of a given idiotype in a population of T cells and the relevant GvH potential of the same T cells that can be visualized are indeed the very same T cells that express immune reactivity against the expected antigens. The present data would thus directly demonstrate the existence of a largely nonoverlapping population of immunocompetent T cells capable of reacting against the various Ag-B locus antigens in the rat. Highly purified, functionally intact immunocompetent T lymphocytes with restricted immune reactivity can thus be produced from normal lymphocyte populations for further analysis.


Author(s):  
Mohammad Rafiee Monjezi ◽  
Hamed Fouladseresht ◽  
Shirin Farjadian ◽  
Behrouz Gharesi-Fard ◽  
Shahdad Khosropanah ◽  
...  

Background: Diabetes increases the risk of myocardial infarction (MI) by 2 to 3 folds. T-lymphocytes play a role in atherosclerosis, which is the main pathology behind MI. Cellular immune responses to beta-2 glycoprotein I (β2GPI) are shown in carotid atherosclerosis. Objective: To investigate the self-reactive, β2GPI-specific T-lymphocytes in patients with and without diabetes and atherosclerosis. Methods: Collectively, 164 subjects with and without diabetes that underwent coronary angiography were divided into four groups based on their diabetes status and coronary stenosis. Group I=Diabetic with ≥50% stenosis: A+D+ (n=66); Group II=Nondiabetic with ≥50% stenosis, A+D- (n=39); Group III=Diabetic with <50% stenosis: A-D+ (n=28); and Group IV=Non-diabetic with <50% stenosis: A-D- (n=31). All groups were evaluated for anti-β2GPI IgG antibody by ELISA method. Then, PBMCs were isolated from 18 subjects and were stimulated with β2GPI-derived peptides to assess their proliferation in accordance with their HLA-DRB1 alleles. Results: Mean β2GPI IgG levels were higher in groups with ≥50% stenosis (A+) compared to those with <50% stenosis (A-), (P=0.02(. Co-presence of diabetes in A+ individuals increased mean β2GPI-specific IgG. Auto-reactive β2GPI-specific T cells were detected in the repertoire of T-lymphocytes in all groups. β2GPI-peptides showed promiscuous restriction by various HLADRB1. Conclusion: β2GPI is the target of cellular and humoral immune responses in patients with atherosclerosis. Since the T cell responses but not antibodies were detectable in A-D+ and A-D- groups, it is reasonable to assume that cellular responses preceded the humoral responses. Post-translation modifications of β2GPI under oxidative and glycemic stresses may have increased the IgG levels in patients with diabetes. Finally, identification of antigens that trigger immuno-pathogenesis in atherosclerosis and diabetes may help development of immunomodulation methods to prevent or treat these debilitating diseases.


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