scholarly journals CD138 Expression Promotes Accumulation and Activation of T Cells in Autoimmune MRL/lpr Mice

2021 ◽  
Author(s):  
Tianhong Xie ◽  
Xin Liu ◽  
Ping Li
Keyword(s):  
T Cells ◽  
Immune System ◽  
Fasl Expression ◽  
Autoreactive T Cells ◽  
Cd69 Expression ◽  
Apoptosis Level ◽  
Self Antigens

Abstract CD138+ T cells that accumulated in Fas-deficiency lupus mice, had been identified as autoreactive T cells in SLE which significantly promoted autoantibody secretion. In present study, we found CD138 expression in T cells played a key role in the progression of SLE in MRL/lpr mice. Our results indicated CD138+ T cells apoptosis was in Fas dependent way. However, CD138 expression of T cells in MRL/lpr mice could significantly prevent T cells apoptosis, contribute to accumulation of T cells and DN T cells and simultaneously promote T cells activation. Importantly, CD138 expression in DN T cells significantly increased FasL expression of DN T cells enhancing the cytotoxity of DN T cells. Phorbol 12-myristate 13-acetate and Ionomycin (PI) stimulation could significantly prevent CD138+ T cells accumulation by strikingly inducing their specific apoptosis. Moreover, PI stimulation significantly activated CD138+ T cells with increased CD69 expression in them. Importantly, our results showed CD69 expression in CD138+ T cells could significantly increase the apoptosis level of them. That indicated PI stimulation could induce specific apoptosis of CD138+ T cells via increasing CD69 expression in CD138+ T cells. In addition, our results showed CD138- T cells in MRL/lpr mice had significant defects in activation. However, to activate T cells could significantly prevent CD138 expression in CD3+ T cells of MRL/lpr mice. Our results suggested CD138 expression in CD3+ T cells of MRL/lpr mice was probably caused by the failure of activation in autoreactive T cells before self-antigens exposure to immune system.

Activated and Expanded T Cells for Potential Therapy of Patients with Autoimmune Diseases.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3854-3854
Author(s):  
Alice Long ◽  
Mark Bonyhadi ◽  
Christophe Ferrand ◽  
Mark Frohlich ◽  
Ronald J. Berenson
Keyword(s):  
T Cells ◽  
Immune System ◽  
T Cell ◽  
Side Effects ◽  
Autoimmune Diseases ◽  
Current Therapy ◽  
High Dose ◽  
Autoreactive T Cells ◽  
Repertoire Analysis ◽  
Tcr Repertoire

Abstract Autoreactive T cells have been implicated as central players in many autoimmune diseases. Current therapy for autoimmune diseases involves chronic immunosuppression, which increases the risk of infection and cancer, and is associated with other side effects. Recently, high-dose chemotherapy combined with stem cell transplantation has been used, but is often associated with severe toxicities. To avoid the side effects associated with these therapies, we are developing an alternative therapeutic approach in which patients are treated with relatively non-toxic therapy to reduce T cell numbers, and then administered healthy T cells to restore the immune system. Most autoimmune patients have oligoclonal populations of T cells as measured by T cell receptor (TCR) repertoire analysis. These may represent autoreactive T cells which contribute to TCR repertoire skewing. Clinical studies have shown a positive correlation between post-therapy TCR repertoire normalization and remission of autoimmune diseases. We have developed the Xcellerate™ Technology for the ex vivo activation and expansion of T cells. To expand T cells, peripheral blood mononuclear cells (PBMCs) are cultured with microscopic paramagnetic beads conjugated with anti-CD3 and anti-CD28 mAbs (Xcyte™Dynabeads®). T cells manufactured using this or a similar technology have been administered to patients with cancer and HIV in several clinical trials. In these studies, we and others have shown that the Xcellerate Technology can normalize skewed TCR repertoires in these patient populations. In the present study, we evaluated the use of the Xcellerate Technology to grow T cells from patients with autoimmune diseases such as rheumatoid arthritis, scleroderma, Crohn’s disease and systemic lupus erythematosus. We collected data on cytokine secretion, activation marker expression, cell expansion and TCR repertoire. T cells expanded an average of 1,325 fold (±1,592; range=16–6,532; n=35 patients), with nearly all cultures displaying marked CD25 and CD154 upregulation, and secretion of high levels of IFNγ and GM-CSF. Similar to results observed in cancer patients, TCR repertoire analysis showed that the Xcellerate Technology can normalize the skewed repertoires observed in autoimmune patients. Out of 12 PBMCs examined by spectratype analysis, one showed no TCR Vβ skewing prior to expansion, whereas the remaining 11 tissues displayed varying degrees of skewedness. After expansion, repertoire skewedness was decreased for all 11 samples. Repertoire normalization was dependent upon high-levels of TCR/CD28 engagement, which was achieved by initiating cultures using high bead to T cell ratios (Figure 1). Neither type of autoimmune disease, disease severity nor patient treatment (including: steroids, melphalan, infliximab, rapamycin, etc.) at the time of blood collection had an adverse effect on the ability to expand the patients’ T cells. Based on these results, the Xcellerate Technology may prove useful for generating healthy T cells from patients with autoimmune diseases which could then be used to restore the immune system following lymphoablative therapy. Studies are underway to further evaluate this approach. Figure Figure

CD4+ and CD8+ autoreactive T cells in narcolepsy patients target self-antigens of hypocretin-producing neurons

immuneACCESS ◽  
2018 ◽  
Author(s):  
D Latorre ◽  
U Kallweit ◽  
E Armentani ◽  
M Foglierini ◽  
F Mele ◽  
...  
Keyword(s):  
T Cells ◽  
Autoreactive T Cells ◽  
Self Antigens

Mechanisms of cooperation between antigenic and cytokine signals in CD8 T cell activation

2016 ◽  
Author(s):  
◽  
Nicholas P. Goplen
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
T Cell Activation ◽  
Cd8 T Cells ◽  
Cell Activation ◽  
White Blood Cells ◽  
Adaptive Immune System ◽  
Inflammatory Proteins ◽  
Self Antigens

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Our adaptive immune system is comprised of white-blood cells that distinguish self- (our own) from foreignproteins (DNA products) and are capable of establishing long-lived immunity against harmful microbes and cancer. One of the cellular subsets that mediate cellular immunity, or protection by distinction, called CD8 T cells, specifically kill only virally infected or cancerous cells. In order to do so, CD8 T cells must integrate signals from the environment that include sensing both small pieces of proteins presented by other immune cells and proteins produced by the inflammatory, or "early-warning", anti-microbial immune response. It is not clear how these two signals (antigen and inflammatory proteins) integrate to activate the cell-mediated immune response that leads to direct killing of infected cells. Answers to how these signals cooperate to activate the immune system, could provide insight into new therapies for caner, autoimmune diseases, and vaccinations. Here, we find specific conditions that lead to activation of CD8 T cells potentially able to respond to self-antigens important for auto-immunity and cancer. Specifically we found that the strength of signal through the receptor that recognizes small pieces of protein, influenced the T cell's ability to sense inflammatory proteins. Further, we found that signals from the inflammatory environment utilize the cell-membrane receptor used to sense small pieces of proteins from self or foreign sources. In an unexpected way response to inflammatory proteins required CD8 T cells to recognize, or sense, self-antigens.

scholarly journals The inability to process a self-peptide allows autoreactive T cells to escape tolerance.

1993 ◽  
Vol 177 (2) ◽  
pp. 567-571 ◽  
Author(s):  
M J Mamula
Keyword(s):  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Cell Response ◽  
T Cell Response ◽  
The Self ◽  
Autoreactive T Cells ◽  
Cyt C ◽  
Antigen Presenting ◽  
Self Peptides

It is now clear that antigen presenting cells (APCs) do not present all the possible peptides of self-proteins to the immune system. When then, is the fate of T cells specific for those self-peptides that escape processing? In this study, the COOH-terminal peptide (residues 81-104) of self cytochrome c (cyt c) elicited strong autoimmune T cells, as well as autoantibodies specific for this immunogen. These T cells did not respond to stimulation with the whole self cyt c molecule, demonstrating that APCs cannot process and present the self 81-104 peptide. Whereas mice were unresponsive to immunization with the whole mouse cyt c molecule, the mouse 81-104 fragment together with the whole self-molecule induced and amplified the autoimmune T cell response to sites within the 1-80 peptide. T cells that never contact the relevant self-peptide are functionally ignorant. They do not become tolerized or deleted, nor do they normally participate in immune responses to the native whole self-protein, since APCs cannot present the 81-104 peptide.

Impact Of Dietary Measures In Autoimmune Diseases

2018 ◽  
Vol 09 (01) ◽  
pp. 01-02
Author(s):  
Nasim Karim
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Autoimmune Diseases ◽  
Autoimmune Response ◽  
Pathogenic Microorganisms ◽  
Body Self ◽  
Self Antigens

The immune system of an individual upon activation by antigens produces response to pathogenic microorganisms their products and to body self-antigens. The latter being known as “Autoimmune Response.” Lymphocytes as T cells and B cells as well as macrophages take part in this response

scholarly journals Microbiota as Drivers and as Therapeutic Targets in Ocular and Tissue Specific Autoimmunity

2021 ◽  
Vol 8 ◽  
Author(s):  
Ryan Salvador ◽  
Amy Zhang ◽  
Reiko Horai ◽  
Rachel R. Caspi
Keyword(s):  
Fatty Acids ◽  
T Cells ◽  
Immune System ◽  
Short Chain Fatty Acids ◽  
Treatment Interventions ◽  
Autoreactive T Cells ◽  
Tissue Specific ◽  
Autoimmune Uveitis ◽  
Commensal Microbiota ◽  
Cellular Measurements

Autoimmune uveitis is a major cause of blindness in humans. Activation of retina-specific autoreactive T cells by commensal microbiota has been shown to trigger uveitis in mice. Although a culprit microbe and/or its immunogenic antigen remains to be identified, studies from inducible and spontaneous mouse models suggest the potential of microbiota-modulating therapies for treating ocular autoimmune disease. In this review, we summarize recent findings on the contribution of microbiota to T cell-driven, tissue-specific autoimmunity, with an emphasis on autoimmune uveitis, and analyze microbiota-altering interventions, including antibiotics, probiotics, and microbiota-derived metabolites (e.g., short-chain fatty acids), which have been shown to be effective in other autoimmune diseases. We also discuss the need to explore more translational animal models as well as to integrate various datasets (microbiomic, transcriptomic, proteomic, metabolomic, and other cellular measurements) to gain a better understanding of how microbiota can directly or indirectly modulate the immune system and contribute to the onset of disease. It is hoped that deeper understanding of these interactions may lead to more effective treatment interventions.

Apoptosis and proliferation ofperipheral blood T-cells as alternative processes in pathogenesis of diabetes mellitus type 1

2019 ◽  
Vol 1 (4) ◽  
pp. 16-20 ◽  
Author(s):  
A. V. Lugovaya ◽  
N. M. Kalinina ◽  
V. Ph. Mitreikin ◽  
Yu. P. Kovaltchuk ◽  
A. V. Artyomova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
T Cells ◽  
High Risk ◽  
Peripheral Blood ◽  
Cellular Response ◽  
Proliferative Potential ◽  
Autoreactive T Cells ◽  
Alternative Processes

Apoptosis, along with proliferation, is a form of lymphocyte response to activating stimuli. In the early stages of cell differentiation, the apoptotic response prevails and it results to the formation of tolerance to inductor antigen. Mature lymphocytes proliferate in response to stimulation and it means the initial stage in the development of the immune response. Since in this case apoptosis and proliferation acts as alternative processes, their ratio can serve as a measure of the effectiveness of the cellular response to activating signals. The resistance of autoreactive T-cells to apoptosis is the main key point in the development of type 1 diabetes mellitus (T1DM). Autoreactive T-cells migrates from the bloodstream to the islet tissue of the pancreas and take an active part in b cells destruction. The resistance of autoreactive effector T-cells to apoptosis may suggest their high proliferative potential. Therefore, the comparative evaluation of apoptosis and proliferation of peripheral blood lymphocytes can give a more complete picture of their functional state and thus will help to reveal the causes of ineffective peripheral blood T-ceiis apoptosis in patients with T1DM and will help to understand more deeply the pathogenesis of the disease. in this article, the features of proliferative response of peripheral blood T-cells in patients with T1DM and in individuals with high risk of developing T1DM have been studied. Apoptosis of T-cell subpopulations has been investigated. The correlation between the apoptotic markers and the intensity of spontaneous and activation- induced in vitro T-cells proliferation of was revealed. it was determined, that autoreactive peripheral blood T-cells were resistant to apoptosis and demonstrated the increased proliferative potential in patients with T1DM and in individuals with high risk of developing T1DM.

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