scholarly journals An identical mechanism governs self-nonself discrimination and effector class regulation

2017 ◽  
Author(s):  
David Usharauli ◽  
Tirumalai Kamala
Keyword(s):  
T Cells ◽  
Immune System ◽  
Regulatory T Cells ◽  
Effective Response ◽  
Commensal Microbiota ◽  
The Past

Prevailing immunological dogma dictates self-nonself discrimination, meaning to respond or not, and effector class regulation, meaning choosing the most effective response, are two separate decisions the immune system makes when faced with a new antigen. Representing a cardinal departure from the past, our model instead predicts both self-nonself discrimination and effector class regulation are in fact one and the same process controlled by Foxp3+ regulatory T cells (Tregs) whose antigen-specific repertoire is entirely maintained by commensal microbiota-derived cross-reactive antigens.

scholarly journals An identical mechanism governs self-nonself discrimination and effector class regulation

2017 ◽  
Author(s):  
David Usharauli ◽  
Tirumalai Kamala
Keyword(s):  
T Cells ◽  
Immune System ◽  
Regulatory T Cells ◽  
Effective Response ◽  
Commensal Microbiota ◽  
The Past

Prevailing immunological dogma dictates self-nonself discrimination, meaning to respond or not, and effector class regulation, meaning choosing the most effective response, are two separate decisions the immune system makes when faced with a new antigen. Representing a cardinal departure from the past, our model instead predicts both self-nonself discrimination and effector class regulation are in fact one and the same process controlled by Foxp3+ regulatory T cells (Tregs) whose antigen-specific repertoire is entirely maintained by commensal microbiota-derived cross-reactive antigens.

scholarly journals Regulatory T Cells, a Potent Immunoregulatory Target for CAM Researchers: The Ultimate Antagonist (I)

2006 ◽  
Vol 3 (1) ◽  
pp. 25-30 ◽  
Author(s):  
Aristo Vojdani ◽  
Jonathan Erde
Keyword(s):  
T Cells ◽  
Immune System ◽  
Regulatory T Cells ◽  
Host Defense ◽  
Western Medicine ◽  
Treg Cells ◽  
Active Suppression ◽  
Beneficial Effects ◽  
The Past ◽  
Powerful Means

Over the past decade, great interest has been given to regulatory T (Treg) cells. A vast body of evidence has shown the existence and highlighted the importance of Treg cells in the active suppression of immune system responses. This form of immunoregulation is the dominant means utilized by the immune system to reach a harmony between reciprocal response processes in order to ensure adequate host defense with minimal host detriment. Therapeutically targeting Treg cells is a direct and powerful means to manipulate the immune system to achieve beneficial effects on various disease pathologies, including allergy, autoimmunity and cancer, as well as the facilitation of organ transplantation. This powerful target for immunoregulation is of much concern to practitioners and researchers of complementary and alternative medicine because it allows a great deal of control and certainty in dealing with the prevalence of debilitating immune system-related disorders for which there has been little remedy outside of Western Medicine.

scholarly journals Requirement of full TCR repertoire for regulatory T cells to maintain intestinal homeostasis

2015 ◽  
Vol 112 (41) ◽  
pp. 12770-12775 ◽  
Author(s):  
Junko Nishio ◽  
Minato Baba ◽  
Koji Atarashi ◽  
Takeshi Tanoue ◽  
Hideo Negishi ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Regulatory T Cells ◽  
Critical Role ◽  
Cell Receptor ◽  
Peripheral Tolerance ◽  
Intestinal Homeostasis ◽  
Commensal Microbiota ◽  
Wide Range ◽  
Tcr Repertoire

The regulation of intestinal homeostasis by the immune system involves the dynamic interplay between gut commensal microbiota and resident immune cells. It is well known that a large and diverse lymphocyte antigen receptor repertoire enables the immune system to recognize and respond to a wide range of invading pathogens. There is also an emerging appreciation for a critical role the T-cell receptor (TCR) repertoire serves in the maintenance of peripheral tolerance by regulatory T cells (Tregs). Nevertheless, how the diversity of the TCR repertoire in Tregs affects intestinal homeostasis remains unknown. To address this question, we studied mice whose T cells express a restricted TCR repertoire. We observed the development of spontaneous colitis, accompanied by the induction of T-helper type 17 cells in the colon that is driven by gut commensal microbiota. We provide further evidence that a restricted TCR repertoire causes a loss of tolerogenicity to microbiota, accompanied by a paucity of peripherally derived, Helios− Tregs and hyperactivation of migratory dendritic cells. These results thus reveal a new facet of the TCR repertoire in which Tregs require a diverse TCR repitoire for intestinal homeostasis, suggesting an additional driving force in the evolutional significance of the TCR repertoire.

scholarly journals Blockade of interleukin-27 signaling reduces GVHD in mice by augmenting Treg reconstitution and stabilizing Foxp3 expression

Blood ◽  
2016 ◽  
Vol 128 (16) ◽  
pp. 2068-2082 ◽  
Author(s):  
Ludovic Belle ◽  
Kimberle Agle ◽  
Vivian Zhou ◽  
Cheng Yin-Yuan ◽  
Richard Komorowski ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Regulatory T Cells ◽  
Foxp3 Expression ◽  
Interleukin 27 ◽  
Key Points ◽  
The Stability

Key Points Blockade of IL-27 signaling mitigates the severity of GVHD by recalibrating the effector and regulatory arms of the immune system. Inhibition of IL-27 augments the reconstitution of CD4+ and CD8+ regulatory T cells and increases the stability of Foxp3 expression.

The role of cytokines in immunological tolerance: potential for therapy

2000 ◽  
Vol 2 (9) ◽  
pp. 1-20 ◽  
Author(s):  
Mark Harber ◽  
Anette Sundstedt ◽  
David Wraith
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Animal Models ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Immunological Tolerance ◽  
Immunomodulatory Effects ◽  
Clinical Potential

Current immunosuppression protocols, although often effective, are nonspecific and therefore hazardous. Consequently, immunological tolerance that is antigen specific and does not globally depress the patient's immune system has become one of the Holy Grails of immunology. Since the discovery that cytokines have immunomodulatory effects, extensive research has investigated the potential of these molecules to induce and maintain specific immunological tolerance in the context of transplantation, allergy and autoimmunity. In this article, we review the possible mechanisms by which cytokines can modulate the immune response and the animal models that frequently confound the theory that a single cytokine, or group of cytokines, can induce tolerance in a predictable manner. Finally, we discuss the role of cytokines at a paracrine level, particularly in the context of inducing and maintaining antigen-specific, regulatory T cells with the clinical potential to suppress specific immune responses.

scholarly journals The Microbiota and Epigenetic Regulation of T Helper 17/Regulatory T Cells: In Search of a Balanced Immune System

2017 ◽  
Vol 8 ◽  
Author(s):  
Annie Luo ◽  
Steven T. Leach ◽  
Romain Barres ◽  
Luke B. Hesson ◽  
Michael C. Grimm ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
Regulatory T Cells ◽  
Epigenetic Regulation ◽  
T Helper ◽  
T Helper 17
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