scholarly journals Allergic Disease and Autoimmune Effectors Pathways

2002 ◽  
Vol 9 (3) ◽  
pp. 161-167 ◽  
Author(s):  
Menachem Rottem ◽  
M. Eric Gershwin ◽  
Yehuda Shoenfeld
Keyword(s):  
T Cells ◽  
Immune System ◽  
Mast Cells ◽  
Cell Receptor ◽  
Common Mechanism ◽  
Common Disease ◽  
Immune Reactivity ◽  
Autoimmune Conditions ◽  
Autoimmune Processes ◽  
Effector Pathways

Allergy and autoimmunity result from dysregulation of the immune system. Until recently, it was generally accepted that the mechanisms that govern these disease processes are quite disparate; however, new discoveries suggest possible common pathogenetic effector pathways. This review illustrates the concomitant presentation of these conditions and the potential relationship or common mechanism in some cases, by looking at the key elements that regulate the immune response in both allergic and autoimmunite conditions: mast cells, antibodies, T cells, cytokines, and genetic determinants. The parallel appearance of allergic and autoimmune conditions in the some patients may reveal that such aberrations of the immune system have a common pathophysiologic mechanism. Mast cells, which play a key role in allergic reactions, and the wealth of inflammatory mediators they express, make it likely that they have profound effects on many autoimmune processes. Activation of protein kinases by inflammatory cytokines and environmental stresses may contribute to both allergic and autoimmune diseases. The presence of autoantibodies in some allergic conditions suggests an autoimmune basis for these conditions. Because of the central role T cells play in immune reactivity, the T-cell receptor (TCR) loci have long been considered important candidates for common disease susceptibility within the immune system such as asthma, atopy, and autoimmunity. Immunomodulation is the key to a successful treatment of allergic and autoimmune conditions.

scholarly journals Human placental villi immune cells help maintain homeostasis in utero

2021 ◽  
Author(s):  
Liza Konnikova ◽  
Jessica M Toothaker ◽  
Oluwabunmi Olaloye ◽  
Blake T McCourt ◽  
Collin C McCourt ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Immune Cells ◽  
Cell Receptor ◽  
In Utero ◽  
Healthy Pregnancy ◽  
Placental Villi ◽  
Fetal Organs ◽  
Antigen Presenting ◽  
With Memory

Maintenance of healthy pregnancy is reliant on successful balance between the fetal and maternal immune systems. Although maternal mechanisms responsible have been well studied, those used by the fetal immune system remain poorly understood. Using suspension mass cytometry and various imaging modalities, we report a complex immune system within the mid-gestation (17-23 weeks) human placental villi (PV). Further, we identified immunosuppressive signatures in innate immune cells and antigen presenting cells that potentially maintain immune homeostasis in utero. Consistent with recent reports in other fetal organs, T cells with memory phenotypes were detected within the PV tissue and vasculature. Moreover, we determined PV T cells could be activated to upregulate CD69 and proliferate after T cell receptor (TCR) stimulation and when exposed to maternal uterine antigens. Finally, we report that cytokine production by PV T cells is sensitive to TCR stimulation and varies between mid-gestation, preterm (26-35 weeks) and term deliveries (37-40 weeks). Collectively, we elucidated the complexity and functional maturity of fetal immune cells within the PV and highlighted their immunosuppressive potential.

scholarly journals Predictable αβ T-Cell Receptor Selection toward an HLA-B*3501-Restricted Human Cytomegalovirus Epitope

2007 ◽  
Vol 81 (13) ◽  
pp. 7269-7273 ◽  
Author(s):  
Rebekah M. Brennan ◽  
John J. Miles ◽  
Sharon L. Silins ◽  
Melissa J. Bell ◽  
Jacqueline M. Burrows ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
T Cell Receptor ◽  
Human Cytomegalovirus ◽  
Clinical Immunology ◽  
Cell Receptor ◽  
Cell Populations ◽  
Tcr Repertoire ◽  
Pp65 Antigen

ABSTRACT Human cytomegalovirus (HCMV) elicits a very large burden on the immune system, with approximately one in ten T cells being reserved solely to manage this infection. However, information on the clonotypic composition of these vast T-cell populations is limited. In this study, we sequenced 116 T-cell receptor (TcR) α/β-chains specific for the highly immunogenic HLA-B*3501-resticted epitope IPSINVHHY from the pp65 antigen. Interestingly, T cells recovered from all donors bore an identical or near-identical TRBV28/TRBJ1-4/TRAV17/TRAJ33 TcR. The ability to predict the responding αβ TcR repertoire before viral infection should prove a powerful tool for basic and clinical immunology.

scholarly journals ВПЛИВ ІМУНОМОДУЛЯТОРІВ НА ПОКАЗНИКИ КЛІТИННОГО ІМУНІТЕТУ ЛОШАТ ВЕРХОВИХ ПОРІД

2016 ◽  
Vol 18 (3(71)) ◽  
pp. 45-49
Author(s):  
I.P. Кrytsia
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Lymphocytes ◽  
Functional Activity ◽  
T Helper Cells ◽  
Hematological Parameters ◽  
Immune Reactivity ◽  
T Helper ◽  
Physiological Level ◽  
Helper Cells

To maintain a body at sufficient physiological level the effective functioning of the immune system, which determines the resistance and immune reactivity of animals, is necessary. In our studies in newborn foals indicators of cellular immunity were mature. During the studying of foals of all ages were established the reduction of hematological parameters in animals months of age.The use of immunomodulators prevents the immunodeficiency in animals. Immunomodulators introduction for animals normalizes T–immune system, in particular, increases the number of leucocytes in the blood, lymphocytes of certain populations, especially teofilin–resistant subpopulation of T–helper cells, increases the functional activity of lymphocytes.Under influence of ribotan revealed a trend to the increasing of T–lymphocytes by 0.2 – 1.2% (0.4 – 2.3%), respectively in Purebred Saddle and Ukrainian Saddle breeds. Results of the content of T–helper and T–suppressor cells in foals blood after ribotan administration showed that the use of immunomodulators not only increases the number of T–helper cells, but restores the ratio T–h / T–s, which returned to the optimal rate (1.9). Analyzing the functional status of T–lymphocytes during the application of immunomodulators was found the probable increase of the number of activated T–lymphocytes in Purebred Saddle foals more than 2–fold (P <0.01) and trend to increase of these cells in Ukrainian Saddle foals. In relation to thermostable T–lymphocytes, was note that the trend to the most optimal level of these cells installed in foals after administration of ribotan (values within 3 – 4%). The increasing in number of thermostable T–cells more than 4% indicates an increase power of suppressor T–cells population, indicating the inhibition of T–helper cells, and therefore the production of antibodies. Thus, the use of ribotan in dose of 1 ml / animal for three days leads to an increasing in 1.4 – 4.5% of the number of leukocytes in the blood of experimental group of foals compared with control animals. Under influence of ribotan in the blood of foals increases cell (number of T–lymphocytes in 0.4 – 2.3%) and functional activity (T–active lymphocytes in 2.3 times; P < 0.05) T–immune system. Under influence of cycloferon in the blood of foals increases the functional activity of T–immune system (the number of T–active lymphocytes in 16.7 – 25%; P < 0.05). 

scholarly journals Molecular Basis of a Dominant SARS-CoV-2 Spike-Derived Epitope Presented by HLA-A*02:01 Recognised by a Public TCR

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2646
Author(s):  
Christopher Szeto ◽  
Andrea T. Nguyen ◽  
Christian A. Lobos ◽  
Demetra S. M. Chatzileontiadou ◽  
Dhilshan Jayasinghe ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Molecular Basis ◽  
Cell Epitope ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
T Cell Response ◽  
X Ray Crystallography ◽  
Gene Usage

The data currently available on how the immune system recognises the SARS-CoV-2 virus is growing rapidly. While there are structures of some SARS-CoV-2 proteins in complex with antibodies, which helps us understand how the immune system is able to recognise this new virus; however, we lack data on how T cells are able to recognise this virus. T cells, especially the cytotoxic CD8+ T cells, are critical for viral recognition and clearance. Here we report the X-ray crystallography structure of a T cell receptor, shared among unrelated individuals (public TCR) in complex with a dominant spike-derived CD8+ T cell epitope (YLQ peptide). We show that YLQ activates a polyfunctional CD8+ T cell response in COVID-19 recovered patients. We detail the molecular basis for the shared TCR gene usage observed in HLA-A*02:01+ individuals, providing an understanding of TCR recognition towards a SARS-CoV-2 epitope. Interestingly, the YLQ peptide conformation did not change upon TCR binding, facilitating the high-affinity interaction observed.

scholarly journals Molecular basis of a dominant SARS-CoV-2 Spike-derived epitope presented by HLA-A*02:01 recognised by a public TCR

2021 ◽  
Author(s):  
Christopher Szeto ◽  
Andrea T Nguyen ◽  
Christian A Lobos ◽  
Dimitra SM Chatzileontiadou ◽  
Dhilshan Jayasinghe ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Molecular Basis ◽  
Cell Epitope ◽  
Cd8 T Cell ◽  
Cell Receptor ◽  
T Cell Response ◽  
X Ray Crystallography ◽  
Gene Usage

The data currently available on how the immune system recognizes the SARS-CoV-2 virus is growing rapidly. While there are structures of some SARS-CoV-2 proteins in complex with antibodies, which helps us understand how the immune system is able to recognise this new virus, we are lacking data on how T cells are able to recognize this virus. T cells, especially the cytotoxic CD8+ T cells, are critical for viral recognition and clearance. Here we report the X-ray crystallography structure of a T cell receptor, shared among unrelated individuals (public TCR) in complex with a dominant spike-derived CD8+ T cell epitope (YLQ peptide). We show that YLQ activates a polyfunctional CD8+ T cell response in COVID-19 recovered patients. We detail the molecular basis for the shared TCR gene usage observed in HLA-A*02:01+ individuals, providing an understanding of TCR recognition towards a SARS-CoV-2 epitope. Interestingly, the YLQ peptide conformation did not change upon TCR binding, facilitating the high-affinity interaction observed.

Role of the immune response induced by superantigens in the pathogenesis of microbial infections

Parasitology ◽  
1997 ◽  
Vol 115 (7) ◽  
pp. 67-78 ◽  
Author(s):  
I. MAILLARD ◽  
F. LUTHI ◽  
H. ACHA-ORBEA ◽  
H. DIGGELMANN
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Mhc Class Ii ◽  
Cell Receptor ◽  
Major Influence ◽  
Clonal Deletion ◽  
Microbial Infections ◽  
T Cell Receptor Vβ

Superantigens (SAgs) are microbial proteins which have potent effects on the immune system. They are presented by major histocompatibility complex (MHC) class II molecules and interact with a large number of T cells expressing specific T cell receptor Vβ domains. Encounter of a SAg leads initially to the stimulation and subsequently to the clonal deletion of reactive T cells. SAgs are expressed by a wide variety of microorganisms which use them to exploit the immune system to their own advantage. Bacterial SAgs are exotoxins which are linked to several diseases in humans and animals. A classical example is the toxic shock syndrome in which the massive release of cytokines by SAg-reactive cells is thought to play a major pathogenic role. The best characterized viral SAg is encoded by mouse mammary tumour virus (MMTV) and has proved to have a major influence on the viral life cycle by dramatically increasing the efficiency of viral infection. In this paper, we review the general properties of SAgs and discuss the different types of microorganisms which produce these molecules, with a particular emphasis on the role played by the SAg-induced immune response in the course of microbial infections.

scholarly journals The concurrent maturation of mouse and human thymocytes in human fetal thymus implanted in NIH-beige-nude-xid mice is associated with the reconstitution of the murine immune system.

1993 ◽  
Vol 177 (3) ◽  
pp. 821-832 ◽  
Author(s):  
T R Kollmann ◽  
M M Goldstein ◽  
H Goldstein
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Keyhole Limpet Hemocyanin ◽  
Cell Receptor ◽  
Scid Mice ◽  
Double Positive ◽  
Fetal Thymus

To determine whether the human thymus provides an environment for the maturation of murine T cells, human fetal thymus and liver (hu-thy/liv) were implanted into congenitally athymic NIH-beige-nude-xid (BNX) mice or C.B-17 scid/scid (SCID) mice. 3 mo after implantation, in contrast to the hu-thy/liv implant in SCID mice, which was populated only with human CD4/CD8 single- and double-positive thymocytes, the hu-thy/liv implant in BNX mice contained a chimeric population of human and mouse CD4/CD8 single- and double-positive thymocytes. Immunohistochemical staining of the hu-thy/liv implant in BNX mice indicated that the population of double-positive mouse thymocytes was localized to discrete areas of the human fetal thymus. Quantitative improvements in mouse T cell and immunoglobulin (Ig) G parameters were observed after grafting of the human fetal thymus and liver tissue into BNX mice. In addition, in contrast to the nonimplanted BNX mice, the implanted BNX mice were capable of mounting a keyhole limpet hemocyanin-specific IgG response and their peripheral T cells were responsive to stimulation with mitogens and antibodies directed to the T cell receptor. Furthermore, after in vivo priming, T cells present in lymph nodes of the implanted BNX mice were capable of mounting an antigen-induced in vitro T cell-dependent proliferative response. Thus, concurrent with the continued maturation of human T cells, murine T cells differentiated within the human fetal thymus implanted in the BNX mice and mediated the phenotypic and functional reconstitution of the murine immune system. Mice with a reconstituted immune system that contain a human thymic implant that is infectible with human immunodeficiency virus (HIV) should prove useful in the investigation of T cell maturation in the thymus and in the evaluation of potential HIV vaccines.

scholarly journals Engineered chimeric T cell receptor fusion construct (TRuC)-expressing T cells prevent translational shutdown in SARS-CoV-2-infected cells

2021 ◽  
Author(s):  
Ira Godbole ◽  
Kevin Ciminski ◽  
O. Sascha Yousefi ◽  
Salma Pathan-Chhatbar ◽  
Deniz Saltukoglu ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Cellular Protein ◽  
Single Chain ◽  
Independent Manner ◽  
Fusion Construct ◽  
Infected Cells

SARS-CoV-2, the causative agent of Covid-19, is known to evade the immune system by several mechanisms. This includes the shutdown of the host cellular protein synthesis, which abrogates the induction of antiviral interferon responses. The virus initiates the infection of susceptible cells by binding with its spike protein (S) to the host angiotensin-converting enzyme 2 (ACE2). Here we applied the T cell receptor fusion construct (TRuC) technology to engineer T cells against such infected cells. In our TRuCs an S-binding domain is fused to the CD3ε component of the T cell receptor (TCR) complex, enabling recognition of S-containing cells in an HLA independent manner. This domain either consists of the S-binding part of ACE2 or a single-chain variable fragment of an anti-S antibody. We show that the TRuC T cells are activated by and kill cells that express S of SARS-CoV-2 and its alpha (B.1.1.7) and beta (B.1.351) variants at the cell surface. Treatment of SARS-CoV-2 infected cells with our engineered T cells did not lead to massive cytotoxicity towards the infected cells, but resulted in a complete rescue of the translational shutdown despite ongoing viral replication. Our data show that engineered TRuC T cell products might be used against SARS-CoV-2 by exposing infected cells to the host innate immune system.

T cell receptor δ repertoire in inflamed and noninflamed colon of patients with IBD analyzed by CDR3 spectratyping

2002 ◽  
Vol 282 (6) ◽  
pp. G1024-G1034 ◽  
Author(s):  
Wolfgang Holtmeier ◽  
Andreas Hennemann ◽  
Ekkehard May ◽  
Rainer Duchmann ◽  
Wolfgang F. Caspary
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptor ◽  
Peripheral Blood ◽  
Cell Receptor ◽  
Published Data ◽  
Cell Clones ◽  
Tcr Repertoire ◽  
Autoimmune Conditions ◽  
Inflammatory Bowel

γ/δ T cells might play an important role in autoimmune conditions like inflammatory bowel disease (IBD). In the present study, we characterized the T cell receptor (TCR)-δ repertoire by complementarity determining region 3 (CDR3) spectratyping in the inflamed and noninflamed mucosa and in the peripheral blood of subjects with Crohn's disease and ulcerative colitis. In contrast to previously published data about α/β T cells, we rarely found oligoclonal expansions of γ/δ T cells specific only for the inflamed mucosa. The same dominant γ/δ T cell expansions were also present in the noninflamed colon. Furthermore, the peripheral γ/δ TCR repertoire was oligoclonal but clearly distinct from that in the inflamed intestine. Thus our results do not support a role for antigen-specific γ/δ T cells in IBD, and dominant γ/δ T cells of the peripheral blood are not likely to be derived from the inflamed gut. However, in several patients, the TCR-δ-repertoire was highly diversified, whereas in others we observed a loss of dominant γ/δ T cell clones when inflamed and noninflamed mucosa were compared. In conclusion, those changes indicate that γ/δ T cells might play an important role in a subset of patients with IBD.

scholarly journals Comprehensive assessment of T-cell receptor β-chain diversity in αβ T cells

Blood ◽  
2009 ◽  
Vol 114 (19) ◽  
pp. 4099-4107 ◽  
Author(s):  
Harlan S. Robins ◽  
Paulo V. Campregher ◽  
Santosh K. Srivastava ◽  
Abigail Wacher ◽  
Cameron J. Turtle ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Dna Sequencing ◽  
T Cell Receptor ◽  
Hematopoietic Cell Transplantation ◽  
Adaptive Immune System ◽  
Cell Receptor ◽  
Adaptive Immune ◽  
Αβ T Cells

Abstract The adaptive immune system uses several strategies to generate a repertoire of T- and B-cell antigen receptors with sufficient diversity to recognize the universe of potential pathogens. In αβ T cells, which primarily recognize peptide antigens presented by major histocompatibility complex molecules, most of this receptor diversity is contained within the third complementarity-determining region (CDR3) of the T-cell receptor (TCR) α and β chains. Although it has been estimated that the adaptive immune system can generate up to 1016 distinct αβ pairs, direct assessment of TCR CDR3 diversity has not proved amenable to standard capillary electrophoresis-based DNA sequencing. We developed a novel experimental and computational approach to measure TCR CDR3 diversity based on single-molecule DNA sequencing, and used this approach to determine the CDR3 sequence in millions of rearranged TCRβ genes from T cells of 2 adults. We find that total TCRβ receptor diversity is at least 4-fold higher than previous estimates, and the diversity in the subset of CD45RO+ antigen-experienced αβ T cells is at least 10-fold higher than previous estimates. These methods should prove valuable for assessment of αβ T-cell repertoire diversity after hematopoietic cell transplantation, in states of congenital or acquired immunodeficiency, and during normal aging.

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