scholarly journals Pathogen-specific regulatory T cells delay the arrival of effector T cells in the lung during early tuberculosis

2010 ◽  
Vol 207 (7) ◽  
pp. 1409-1420 ◽  
Author(s):  
Shahin Shafiani ◽  
Glady’s Tucker-Heard ◽  
Ai Kariyone ◽  
Kiyoshi Takatsu ◽  
Kevin B. Urdahl
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Initial Phase ◽  
Adaptive Immune System ◽  
Effector T Cells ◽  
Primary Site ◽  
Bacterial Burden ◽  
Adaptive Immune ◽  
Pulmonary Lymph Node

The ability of the adaptive immune system to restrict Mycobacterium tuberculosis (Mtb) is impeded by activated Foxp3+ regulatory T (T reg) cells. The importance of pathogen-specific T reg cells in this process has not been addressed. We show that T reg cell expansion after aerosol Mtb infection does not occur until Mtb is transported to the pulmonary lymph node (pLN), and Mtb-specific T reg cells have an increased propensity to proliferate. Even small numbers of Mtb-specific T reg cells are capable of delaying the priming of effector CD4+ and CD8+ T cells in the pLN and their subsequent accumulation in the lung, the primary site of infection. This delay likely prolongs the initial phase of bacterial expansion and explains the higher bacterial burden observed in these mice. Thus, T reg cells recognizing Mtb-derived antigens specifically and potently restrict protective immune responses during tuberculosis.

scholarly journals 62: Sensing and Alarm Function of Mucosal Memory CD8 T Cells Trigger Innate and Adaptive Immune Responses

2015 ◽  
Vol 143 (suppl_1) ◽  
pp. A034-A034 ◽  
Author(s):  
Jason M. Schenkel ◽  
Kathryn A. Fraser ◽  
Lalit K. Beura ◽  
Kristen E. Pauken ◽  
David Masopust ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Adaptive Immune Responses ◽  
Memory Cd8 T Cells ◽  
Adaptive Immune

scholarly journals Human plasmacytoid dendritic cells efficiently cross-present exogenous Ags to CD8+ T cells despite lower Ag uptake than myeloid dendritic cell subsets

Blood ◽  
2013 ◽  
Vol 121 (3) ◽  
pp. 459-467 ◽  
Author(s):  
Jurjen Tel ◽  
Gerty Schreibelt ◽  
Simone P. Sittig ◽  
Till S. M. Mathan ◽  
Sonja I. Buschow ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Adaptive Immune System ◽  
Plasmacytoid Dendritic Cells ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Antitumor Immunotherapy

Abstract In human peripheral blood, 4 populations of dendritic cells (DCs) can be distinguished, plasmacytoid dendritic cells (pDCs) and CD16+, CD1c+, and BDCA-3+ myeloid DCs (mDCs), each with distinct functional characteristics. DCs have the unique capacity to cross-present exogenously encountered antigens (Ags) to CD8+ T cells. Here we studied the ability of all 4 blood DC subsets to take up, process, and present tumor Ags to T cells. Although pDCs take up less Ags than CD1c+ and BDCA3+ mDCs, pDCs induce potent Ag-specific CD4+ and CD8+ T-cell responses. We show that pDCs can preserve Ags for prolonged periods of time and on stimulation show strong induction of both MHC class I and II, which explains their efficient activation of both CD4+ and CD8+ T cells. Furthermore, pDCs cross-present soluble and cell-associated tumor Ags to cytotoxic T lymphocytes equally well as BDCA3+ mDCs. These findings, and the fact that pDCs outnumber BDCA3+ mDCs, both in peripheral blood and lymph nodes, together with their potent IFN-I production, known to activate both components of the innate and adaptive immune system, put human pDCs forward as potent activators of CD8+ T cells in antitumor responses. Our findings may therefore have important consequences for the development of antitumor immunotherapy.

scholarly journals The Modulation of Adaptive Immune Responses by Bacterial Zwitterionic Polysaccharides

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Tom Li Stephen ◽  
Laura Groneck ◽  
Wiltrud Maria Kalka-Moll
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Antigen Processing ◽  
Adaptive Immune System ◽  
Microbial Pathogens ◽  
Adaptive Immune ◽  
Inflammatory Conditions ◽  
Adaptive Immune Cells ◽  
Zwitterionic Polysaccharides

The detection of pathogen-derived molecules as foreign particles by adaptive immune cells triggers T and B lymphocytes to mount protective cellular and humoral responses, respectively. Recent immunological advances elucidated that proteins and some lipids are the principle biological molecules that induce protective T cell responses during microbial infections. Polysaccharides are important components of microbial pathogens and many vaccines. However, research concerning the activation of the adaptive immune system by polysaccharides gained interest only recently. Traditionally, polysaccharides were considered to be T cell-independent antigens that did not directly activate T cells or induce protective immune responses. Here, we review several recent advances in “carbohydrate immunobiology”. A group of bacterial polysaccharides that are known as “zwitterionic polysaccharides (ZPSs)” were recently identified as potent immune modulators. The immunomodulatory effect of ZPSs required antigen processing and presentation by antigen presenting cells, the activation of CD4 T cells and subpopulations of CD8 T cells and the modulation of host cytokine responses. In this review, we also discuss the potential use of these unique immunomodulatory ZPSs in new vaccination strategies against chronic inflammatory conditions, autoimmunity, infectious diseases, allergies and asthmatic conditions.

scholarly journals Comparative ability of IL-12 and IL-28B to regulate Treg populations and enhance adaptive cellular immunity

Blood ◽  
2009 ◽  
Vol 113 (23) ◽  
pp. 5868-5877 ◽  
Author(s):  
Matthew P. Morrow ◽  
Panyupa Pankhong ◽  
Dominick J. Laddy ◽  
Kimberly A. Schoenly ◽  
Jian Yan ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Dna Vaccination ◽  
Vaccine Adjuvant ◽  
Cell Populations ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Strong Candidate ◽  
First Time

Abstract Improving the potency of immune responses is paramount among issues concerning vaccines against deadly pathogens. IL-28B belongs to the newly described interferon lambda (IFNλ) family of cytokines, and has not yet been assessed for its potential ability to influence adaptive immune responses or act as a vaccine adjuvant. We compared the ability of plasmid-encoded IL-28B to boost immune responses to a multiclade consensus HIV Gag plasmid during DNA vaccination with that of IL-12. We show here that IL-28B, like IL-12, is capable of robustly enhancing adaptive immunity. Moreover, we describe for the first time how IL-28B reduces regulatory T-cell populations during DNA vaccination, whereas IL-12 increases this cellular subset. We also show that IL-28B, unlike IL-12, is able to increase the percentage of splenic CD8+ T cells in vaccinated animals, and that these cells are more granular and have higher antigen-specific cytolytic degranulation compared with cells taken from animals that received IL-12 as an adjuvant. Lastly, we report that IL-28B can induce 100% protection from mortality after a lethal influenza challenge. These data suggest that IL-28B is a strong candidate for further studies of vaccine or immunotherapy protocols.

scholarly journals Egr2 and 3 control adaptive immune responses by temporally uncoupling expansion from T cell differentiation

2017 ◽  
Vol 214 (6) ◽  
pp. 1787-1808 ◽  
Author(s):  
Tizong Miao ◽  
Alistair L.J. Symonds ◽  
Randeep Singh ◽  
Janine D. Symonds ◽  
Ane Ogbe ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Clonal Expansion ◽  
Effector T Cells ◽  
T Cell Differentiation ◽  
Fundamental Function ◽  
Adaptive Immune ◽  
Expression Of Genes ◽  
Proliferation And Differentiation ◽  
Upstream Regulators

Egr2 and 3 are important for maintaining immune homeostasis. Here we define a fundamental function of Egr2 and 3 operating as a checkpoint that controls the transition between clonal expansion and differentiation of effector T cells. Egr2 and 3 deficiency resulted in defective clonal expansion but hyperactivation and excessive differentiation of T cells in response to viral infection. Conversely, sustained Egr2 expression enhanced expansion but severely impaired effector differentiation. Egr2 bound to and controlled the expression of genes regulating proliferation (Myc and Myb) and differentiation repressors (Bcl6, Id3), while repressing transcription factors required for effector function (Zeb2, RORa, RORc, and Bhlhe40). Egr2 and 3 expression in T cells was regulated reciprocally by antigen and IFNγ, providing a mechanism for adjusting proliferation and differentiation of individual T cells. Thus, Egr2 and 3 are upstream regulators of effector CD4 and CD8 T cells that are essential for optimal responses with limited immunopathology.

Adaptive Immune System in Fish

2021 ◽  
Vol 22 (4) ◽  
Author(s):  
Adef Othan Kordon ◽  
Lesya Pinchuk ◽  
Attila Karsi
Keyword(s):  
T Cells ◽  
Immune System ◽  
Immune Responses ◽  
Teleost Fish ◽  
Cytotoxic T Cells ◽  
Adaptive Immune System ◽  
Immune Memory ◽  
Cellular Cytotoxicity ◽  
Th Cells ◽  
Adaptive Immune

The immune system of all jawed vertebrates is composed of two major subsystems, the innate (non-specific) and adaptive (specific) immune system. The innate immune system is the first to respond to infectious agents; however, it does not provide longlasting protection. The adaptive immune system is activated later and responds to pathogens with specificity and memory. The main components of the adaptive immune system, including T cell receptors (TCRs), major histocompatibility complex (MHC), immunoglobulins (Igs), and recombination-activating gene (RAG) arose in the first jawed fish (cartilaginous and teleost fish). This review explores and discusses components of the adaptive immune system in teleost fish and recent developments in comparative immunology. Similar to mammals, the adaptive immune system in teleost fish is divided into two components: cellular-mediated responses and humoralmediated responses. T cells, the principal elements of cellular-mediated adaptive immune responses, differentiate into effector helper T (Th) cells or effector cytotoxic T cells (CTLs). The central elements involved in the differentiation of Th subsets in mammals, cytokines and master transcription factors, have also been identified in teleost fish. In addition, each subset of Th cells, defined with a particular cytokine to control the immune responses, has been described in teleost fish. Similarly, to mammals, CTLs contribute to cellular cytotoxicity in teleost fish. B cells act as a central player in humoral-mediated adaptive immunity by producing opsonizing, neutralizing and complement-binding antibodies and inducing antibody-dependent cellular cytotoxicity (ADCC). Three classes of antibodies named IgM, IgD, and IgT/Z have been characterized in teleost fish. The presence of an adaptive immune system and consequent immune memory in teleost fish allows vaccination, the most appropriate method for disease control in aquaculture. Immunological studies in fish provide a comprehensive assessment of the fish immune system, which is crucial for understanding the evolution of the mammalian immune system.

scholarly journals Thymosin alpha-1 Protected T Cells from Excessive Activation in Severe COVID-19

2020 ◽  
Author(s):  
Kuai Yu ◽  
Yongjian Wu ◽  
Jingjing He ◽  
Xuefei Liu ◽  
Bo Wei ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Severe Disease ◽  
Adaptive Immune Responses ◽  
Activated T Cells ◽  
Adaptive Immune ◽  
The Impact ◽  
Excessive Activation

Abstract Two typical features of uncontrolled inflammation, cytokine storm and lymphopenia, are associated with the severity of coronavirus disease 2019 (COVID-19), demonstrating that both innate and adaptive immune responses are involved in the development of this disease. Recent studies have explored the contribution of innate immune cells to the pathogenesis of the infection. However, the impact of adaptive immunity on this disease remains unknown. In order to clarify the role of adaptive immune response in COVID-19, we characterized the phenotypes of lymphocytes in PBMCs from patients at different disease stages using single-cell RNA sequencing (scRNA-seq) technology. Dynamics of the effector cell levels in lymphocytes revealed dysregulated adaptive immune responses in patients with severe disease. A new cluster of excessively activated CD8 T cells (Tea) was further identified, which displayed exhausted phenotypes and diminished function of antigen recognition. Interestingly, expression of PTMA, the proprotein of Tα1, was significantly increased in a group of highly proliferating CD8 T cells with memory stem cell features. We further showed that Tα1 significantly promoted the proliferation of activated T cells in vitro and relieved the lymphopenia in COVID-19 patients. Our data suggest that protection of T cells from excessive activation might be critical for the prevention of severe COVID-19.

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