scholarly journals Pathophysiological Roles of Mucosal-Associated Invariant T Cells in the Context of Gut Microbiota-Liver Axis

2021 ◽  
Vol 9 (2) ◽  
pp. 296
Author(s):  
Yoseph Asmelash Gebru ◽  
Mi Ran Choi ◽  
Ganesan Raja ◽  
Haripriya Gupta ◽  
Satya Priya Sharma ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Cell Activation ◽  
Intestinal Barrier ◽  
Antigen Presenting Cells ◽  
Cell Receptor ◽  
Immune Functions ◽  
Human Immune System ◽  
Mait Cells ◽  
Antigen Presenting ◽  
Microbial Biosynthesis

Mucosal-associated invariant T (MAIT) cells are a subset of T lymphocytes expressing a semi-invariant T-cell receptor (TCR) present as TCR Vα7.2-Jα33 in humans and TCR Vα19-Jα33 in mice. They are activated by ligands produced during microbial biosynthesis of riboflavin that is presented by major histocompatibility complex class I-related (MR1) molecules on antigen-presenting cells. MAIT cells also possess interleukin (IL)-12 and IL-18 receptors and can be activated by the respective cytokines released from microbially stimulated antigen-presenting cells. Therefore, MAIT cells can be involved in bacterial and viral defenses and are a significant part of the human immune system. They are particularly abundant in the liver, an organ serving as the second firewall of gut microbes next to the intestinal barrier. Therefore, the immune functions of MAIT cells are greatly impacted by changes in the gut-microbiota and play important roles in the gut-liver pathogenesis axis. In this review, we discuss the nature and mechanisms of MAIT cell activation and their dynamics during different types of liver pathogenesis conditions. We also share our perspectives on important aspects that should be explored further to reveal the exact roles that MAIT cells play in liver pathogenesis in the context of the gut microbiota.

Human mucosal-associated invariant T cells respond to Mucorales species in a MR1-dependent manner

2020 ◽  
Author(s):  
Sarah Böttcher ◽  
Susann Hartung ◽  
Florian Meyer ◽  
Silke Rummler ◽  
Kerstin Voigt ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Activation ◽  
Cell Receptor ◽  
Mucor Circinelloides ◽  
Dependent Manner ◽  
Rhizopus Microsporus ◽  
Mait Cells ◽  
Cd107a Expression ◽  
Invariant T Cells ◽  
Antigen Presenting

Abstract Activation of mucosal-associated invariant T cells (MAIT cells) by certain bacteria, viruses, and yeast is well studied, but the activation potential of filamentous moulds from the order Mucorales is not known. Here, we show a rapid response of human MAIT cells against the Mucorales species Mucor circinelloides, Rhizopus arrhizus, and Rhizopus microsporus. This activation included upregulation of CD69 and degranulation marked by increased CD107a expression, while intracellular perforin and granzyme A expression were reduced. Furthermore, blocking of the antigen-presenting molecule major histocompatibility complex class I-related abrogated MAIT cell activation demonstrating a T cell receptor-dependent stimulation by Mucorales.

Abstract MP51: Isolevuglandins In Antigen-presenting Cells, A Biomarker For Salt Sensitivity Of Blood Pressure In Humans?

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Lale Ertuglu ◽  
Fernando Elijovich ◽  
Melis Sahinoz ◽  
Cheryl L Laffer ◽  
Ashley Pitzer ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Cell Activation ◽  
Renal Medulla ◽  
Antigen Presenting Cells ◽  
Dependent Manner ◽  
Salt Loading ◽  
Elevation Changes ◽  
Salt Depletion ◽  
Positive Correlations ◽  
Antigen Presenting

Background: High Na+ stimulates antigen-presenting cells (APCs) in an ENaC dependent manner, with formation of isolevuglandin (isoLG) adducts (neoantigen peptides) that promote T cell activation and salt sensitive (SS) hypertension in rodents. Methods: We studied this pathway in 9 subjects with essential hypertension who discontinued anti-hypertensive therapy for 2 weeks. Their SS was assessed by 24-hrs of salt loading (460 mmoL) and salt depletion (10 mmoL/24 hr, plus furosemide 40 mg x 3). Muscle and skin Na + were measured at baseline (BA) by 23 Na magnetic resonance imaging (NaMRI). The % of APCs containing isoLG adducts (flow cytometry), urine and serum electrolytes and epoxyeicosatrienoic acids (EETs 8-9, 11-12 and 14-15) were measured at BA, after salt-loading (HI) and after salt-depletion (LO). Results: Age was 54 years (48-56), with 23% female, BMI 30 kg/m 2 (28-40) and screening SBP 136 mmHg (120-144), and DBP 85 mmHg (75-99). BA 24-hr urine Na + excretion was 178 (143-212) mmoL, Hi 392 (229-421) and LO 27 (25-29). SBP response to salt-depletion varied from -13.8 to +5.6 mmHg. Muscle Na+ correlated with duration of hypertension (r=0.73, p<0.03) and with SBP, DBP and mean arterial pressure (MAP) during BA, HI and LO (r=0.66 to 0.87). Mean %isoLGs in APCs were not different among the three stages of the protocol but ΔisoLGs due to HI or LO had positive correlations with ΔSBP, ΔDBP and ΔMAP produced by the same interventions (r=0.46 to 0.70). A 10% change in dendritic cell isoLGs predicted a 1.45 mmHg change of SBP in the same direction. Urine (not plasma) EETs (sum of three isoforms) showed negative correlations with isoLGs on the three phases of the protocol (r=0.57 to 0.69), and ΔEETs by HI and LO correlated negatively with ΔisoLGs produced by the same interventions (r=0.58 to 0.77). Conclusions: Muscle Na+ increases with duration of hypertension and correlates with severity of BP elevation. Changes in APC isoLGs due to Na+ loading or depletion seem to be a biomarker of SS of BP in humans. Relations between urine EETs and ΔEETs with APC isoLGs and ΔisoLGs suggest that EETs might be inhibitors of APC ENaC as they are of renal ENaC. Relationships between isoLGs and urine but not plasma EETs suggest that activation of APCs by high salt may occur in the hyperosmolar renal medulla.

scholarly journals Abortive Proliferation of Rare T Cells Induced by Direct or Indirect Antigen Presentation by Rare B Cells In Vivo

1998 ◽  
Vol 187 (10) ◽  
pp. 1611-1621 ◽  
Author(s):  
Sarah E. Townsend ◽  
Christopher C. Goodnow
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Antigen Presentation ◽  
Cell Fate ◽  
T Cell Activation ◽  
Cell Activation ◽  
Antigen Presenting Cells ◽  
Antigen Presenting

Antigen-specific B cells are implicated as antigen-presenting cells in memory and tolerance responses because they capture antigens efficiently and localize to T cell zones after antigen capture. It has not been possible, however, to visualize the effect of specific B cells on specific CD4+ helper T cells under physiological conditions. We demonstrate here that rare T cells are activated in vivo by minute quantities of antigen captured by antigen-specific B cells. Antigen-activated B cells are helped under these conditions, whereas antigen-tolerant B cells are killed. The T cells proliferate and then disappear regardless of whether the B cells are activated or tolerant. We show genetically that T cell activation, proliferation, and disappearance can be mediated either by transfer of antigen from antigen-specific B cells to endogenous antigen-presenting cells or by direct B–T cell interactions. These results identify a novel antigen presentation route, and demonstrate that B cell presentation of antigen has profound effects on T cell fate that could not be predicted from in vitro studies.

scholarly journals Role of Antigen-Presenting Cells in Mediating Tolerance and Autoimmunity

1999 ◽  
Vol 191 (11) ◽  
pp. 2021-2028 ◽  
Author(s):  
Kristine M. Garza ◽  
Steven M. Chan ◽  
Rakesh Suri ◽  
Linh T. Nguyen ◽  
Bernhard Odermatt ◽  
...  
Keyword(s):  
T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Islet Cells ◽  
Antigen Presenting Cells ◽  
Cell Receptor ◽  
Lymphocytic Choriomeningitis ◽  
Activation Markers ◽  
Insulin Promoter ◽  
Lymphocyte Activity ◽  
Antigen Presenting

The mechanisms that determine whether receptor stimulation leads to lymphocyte tolerance versus activation remain poorly understood. We have used rat insulin promoter (RIP)-gp/P14 double-transgenic mice expressing the lymphocytic choriomeningitis virus (LCMV) glycoprotein (gp) on pancreatic β-islet cells together with T cells expressing an LCMV-gp–specific T cell receptor to assess the requirements for the induction of autoimmunity. Our studies have shown that administration of the gp peptide gp33 leads to the activation of P14-transgenic T cells, as measured by the upregulation of activation markers and the induction of effector cytotoxic activity. This treatment also leads to expansion and deletion of P14 T cells. Despite the induction of cytotoxic T lymphocyte activity, peptide administration is not sufficient to induce diabetes. However, the administration of gp peptide together with an activating anti-CD40 antibody rapidly induces diabetes. These findings suggest that the induction of tolerance versus autoimmunity is determined by resting versus activated antigen-presenting cells.

scholarly journals Augmentation of T-Cell Activation by Oscillatory Forces and Engineered Antigen-Presenting Cells

Nano Letters ◽  
2019 ◽  
Vol 19 (10) ◽  
pp. 6945-6954 ◽  
Author(s):  
Fatemeh S. Majedi ◽  
Mohammad Mahdi Hasani-Sadrabadi ◽  
Timothy J. Thauland ◽  
Song Li ◽  
Louis-S. Bouchard ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Antigen Presenting Cells ◽  
Antigen Presenting

scholarly journals Atypical TRAV1-2− T cell receptor recognition of the antigen-presenting molecule MR1

2020 ◽  
Vol 295 (42) ◽  
pp. 14445-14457 ◽  
Author(s):  
Wael Awad ◽  
Erin W. Meermeier ◽  
Maria L. Sandoval-Romero ◽  
Jérôme Le Nours ◽  
Aneta H. Worley ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
T Cell Repertoire ◽  
Cell Repertoire ◽  
Mait Cells ◽  
Receptor Recognition ◽  
Antigen Presenting ◽  
Β Chain ◽  
Complementarity Determining Region

MR1 presents vitamin B–related metabolites to mucosal associated invariant T (MAIT) cells, which are characterized, in part, by the TRAV1-2+ αβ T cell receptor (TCR). In addition, a more diverse TRAV1-2− MR1-restricted T cell repertoire exists that can possess altered specificity for MR1 antigens. However, the molecular basis of how such TRAV1-2− TCRs interact with MR1–antigen complexes remains unclear. Here, we describe how a TRAV12-2+ TCR (termed D462-E4) recognizes an MR1–antigen complex. We report the crystal structures of the unliganded D462-E4 TCR and its complex with MR1 presenting the riboflavin-based antigen 5-OP-RU. Here, the TRBV29-1 β-chain of the D462-E4 TCR binds over the F′-pocket of MR1, whereby the complementarity-determining region (CDR) 3β loop surrounded and projected into the F′-pocket. Nevertheless, the CDR3β loop anchored proximal to the MR1 A′-pocket and mediated direct contact with the 5-OP-RU antigen. The D462-E4 TCR footprint on MR1 contrasted that of the TRAV1-2+ and TRAV36+ TCRs' docking topologies on MR1. Accordingly, diverse MR1-restricted T cell repertoire reveals differential docking modalities on MR1, thus providing greater scope for differing antigen specificities.

Antibody Inhibition of HIV-1 Transmission from Antigen-presenting Cells to CD4 T Lymphocytes Involves Immune Cell Activation

2014 ◽  
Vol 30 (S1) ◽  
pp. A154-A154
Author(s):  
Bin Su ◽  
Alexandre Lederle ◽  
Géraldine Laumond ◽  
Sylvie Schmidt ◽  
Thomas Decoville ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cell Activation ◽  
Immune Cell ◽  
Antigen Presenting Cells ◽  
Immune Cell Activation ◽  
Antigen Presenting ◽  
Antibody Inhibition ◽  
Hiv 1
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