scholarly journals Activation of NKT Cells Protects Mice from Tuberculosis

2002 ◽  
Vol 70 (11) ◽  
pp. 6302-6309 ◽  
Author(s):  
Alissa Chackerian ◽  
Jen Alt ◽  
Vaji Perera ◽  
Samuel M. Behar
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Tissue Injury ◽  
Adaptive Immune Response ◽  
Nkt Cells ◽  
Cell Immune Response ◽  
Class I Mhc ◽  
Mhc I ◽  
Mhc Ii

ABSTRACT The T-cell immune response to Mycobacterium tuberculosis is critical in preventing clinical disease. While it is generally accepted that both major histocompatibility complex class I (MHC-I)-restricted CD8+ and MHC-II-restricted CD4+ T cells are important for the immune response to M. tuberculosis, the role of non-MHC-restricted T cells is still not clearly delineated. We have previously reported that CD1d−/− mice do not differ from CD1d+/+ mice in their survival following infection with M. tuberculosis. We now show that, although CD1d-restricted NKT cells are not required for optimum immunity to M. tuberculosis, specific activation of NKT cells by the CD1d ligand α-galactosylceramide protects susceptible mice from tuberculosis. Treatment with α-galactosylceramide reduced the bacterial burden in the lungs, diminished tissue injury, and prolonged survival of mice following inoculation with virulent M. tuberculosis. The capacity of activated NKT cells to stimulate innate immunity and modulate the adaptive immune response to promote a potent antimicrobial immune response suggests that α-galactosylceramide administration could have a role in new strategies for the therapy of infectious diseases.

scholarly journals Role of the cellular immunity in the formation of the immune response in coronavirus infections

2021 ◽  
Vol 23 (6) ◽  
pp. 1229-1238
Author(s):  
I. A. Ivanova ◽  
N. D. Omelchenko ◽  
A. V. Filippenko ◽  
A. A. Trufanova ◽  
A. K. Noskov
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cellular Immunity ◽  
Memory T Cells ◽  
Adaptive Immune Response ◽  
Cell Immune Response ◽  
Adaptive Immune ◽  
Specific Memory ◽  
Causative Agents

The data obtained during previous epidemics caused by coronaviruses, and current pandemic indicate that assessing the role of certain immune interactions between these viruses and the microorganism is the main pre-requisite for development of diagnostic test systems as well as effective medical drugs and preventive measures. The review summarizes the results of studying patho– and immunogenesis of SARSCoV, MERS-CoV, and SARS-CoV-2 infections. These coronaviruses were proven to suppress development of adaptive immune response at the stage of its induction, affecting the number and functional activity of lymphocytes, effectors of cellular immunity, causing impairment of lymphopoiesis, apoptosis and «depletion» of these cells, thus leading to longer duration of the disease and increased viral load. Information about the role of cellular immunity in development of immune response to coronaviruses is presented. It was proven that the causative agents of SARS, MERS and COVID-19 trigger adaptive immune response in the microorganism according to both humoral and cellular types. Moreover, the synthesis of specific immunoglobulins does not yet point to presence of protective immune response. Activation of the cellular link of immunity is also important. A high degree of antigenic epitope homology in SARS-CoV, MERS-CoV and SARS-CoV-2 is described, thus suggesting an opportunity for cross-immunity to coronaviruses. The review addresses issues related to the terms of specific memory immune cells to SARS-CoV, MERS-CoV and SARS-CoV-2, and their role in providing long-term protection against these infections. Given that specific antibodies to SARS and MERS pathogens persisted for a year, were often not detected or briefly registered in patients with mild and asymptomatic infections, we can talk about important role of the cellular immune response in providing immunity to these coronaviruses. It was shown that, in contrast to antibodies, the antigen-specific memory T cells were registered in patients with SARS virus for 4 to 11 years, and Middle East Respiratory Syndrome – up to two years. Further research is needed to determine presence and number of memory T cells in COVID-19. A comparative analysis of data obtained during previous epidemics with respect to formation of adaptive immunity to coronaviruses. Description of proteins and epitopes recognized by human T lymphocytes will be useful in monitoring immune responses in COVID-19 patients, as well as in developing informative tests to study T cell immune response to SARS-CoV-2 and new preventive drugs.

scholarly journals Type I Natural Killer T Cells as Key Regulators of the Immune Response to Infectious Diseases

2020 ◽  
Vol 34 (2) ◽  
pp. e00232-20
Author(s):  
Nicolás M. S. Gálvez ◽  
Karen Bohmwald ◽  
Gaspar A. Pacheco ◽  
Catalina A. Andrade ◽  
Leandro J. Carreño ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Infectious Diseases ◽  
Natural Killer ◽  
Nkt Cells ◽  
Interleukin 4 ◽  
Type I ◽  
Inkt Cells ◽  
Class I Mhc ◽  
Natural Killer T

SUMMARYThe immune system must work in an orchestrated way to achieve an optimal response upon detection of antigens. The cells comprising the immune response are traditionally divided into two major subsets, innate and adaptive, with particular characteristics for each type. Type I natural killer T (iNKT) cells are defined as innate-like T cells sharing features with both traditional adaptive and innate cells, such as the expression of an invariant T cell receptor (TCR) and several NK receptors. The invariant TCR in iNKT cells interacts with CD1d, a major histocompatibility complex class I (MHC-I)-like molecule. CD1d can bind and present antigens of lipid nature and induce the activation of iNKT cells, leading to the secretion of various cytokines, such as gamma interferon (IFN-γ) and interleukin 4 (IL-4). These cytokines will aid in the activation of other immune cells following stimulation of iNKT cells. Several molecules with the capacity to bind to CD1d have been discovered, including α-galactosylceramide. Likewise, several molecules have been synthesized that are capable of polarizing iNKT cells into different profiles, either pro- or anti-inflammatory. This versatility allows NKT cells to either aid or impair the clearance of pathogens or to even control or increase the symptoms associated with pathogenic infections. Such diverse contributions of NKT cells to infectious diseases are supported by several publications showing either a beneficial or detrimental role of these cells during diseases. In this article, we discuss current data relative to iNKT cells and their features, with an emphasis on their driving role in diseases produced by pathogenic agents in an organ-oriented fashion.

scholarly journals Cytotoxic CD8+T lymphocytes expressing ALS-causing SOD1 mutant selectively trigger death of spinal motoneurons

2019 ◽  
Vol 116 (6) ◽  
pp. 2312-2317 ◽  
Author(s):  
Emmanuelle Coque ◽  
Céline Salsac ◽  
Gabriel Espinosa-Carrasco ◽  
Béla Varga ◽  
Nicolas Degauque ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Interaction Strength ◽  
Adaptive Immune Response ◽  
Clonal Diversity ◽  
Mhc I ◽  
Mutant Sod1 ◽  
Cytotoxicity Activity

Adaptive immune response is part of the dynamic changes that accompany motoneuron loss in amyotrophic lateral sclerosis (ALS). CD4+T cells that regulate a protective immunity during the neurodegenerative process have received the most attention. CD8+T cells are also observed in the spinal cord of patients and ALS mice although their contribution to the disease still remains elusive. Here, we found that activated CD8+T lymphocytes infiltrate the central nervous system (CNS) of a mouse model of ALS at the symptomatic stage. Selective ablation of CD8+T cells in mice expressing the ALS-associated superoxide dismutase-1 (SOD1)G93Amutant decreased spinal motoneuron loss. Using motoneuron-CD8+T cell coculture systems, we found that mutant SOD1-expressing CD8+T lymphocytes selectively kill motoneurons. This cytotoxicity activity requires the recognition of the peptide-MHC-I complex (where MHC-I represents major histocompatibility complex class I). Measurement of interaction strength by atomic force microscopy-based single-cell force spectroscopy demonstrated a specific MHC-I-dependent interaction between motoneuron andSOD1G93ACD8+T cells. Activated mutant SOD1 CD8+T cells produce interferon-γ, which elicits the expression of the MHC-I complex in motoneurons and exerts their cytotoxic function through Fas and granzyme pathways. In addition, analysis of the clonal diversity of CD8+T cells in the periphery and CNS of ALS mice identified an antigen-restricted repertoire of their T cell receptor in the CNS. Our results suggest that self-directed immune response takes place during the course of the disease, contributing to the selective elimination of a subset of motoneurons in ALS.

scholarly journals The critical role of CD4+ T cells in PD-1 blockade against MHC-II–expressing tumors such as classic Hodgkin lymphoma

2020 ◽  
Vol 4 (17) ◽  
pp. 4069-4082
Author(s):  
Joji Nagasaki ◽  
Yosuke Togashi ◽  
Takeaki Sugawara ◽  
Makiko Itami ◽  
Nobuhiko Yamauchi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Critical Role ◽  
Cd4 T Cell ◽  
Antitumor Effects ◽  
Cell Axis ◽  
Mhc I ◽  
Mhc Ii

Abstract Classic Hodgkin lymphoma (cHL) responds markedly to PD-1 blockade therapy, and the clinical responses are reportedly dependent on expression of major histocompatibility complex class II (MHC-II). This dependence is different from other solid tumors, in which the MHC class I (MHC-I)/CD8+ T-cell axis plays a critical role. In this study, we investigated the role of the MHC-II/CD4+ T-cell axis in the antitumor effect of PD-1 blockade on cHL. In cHL, MHC-I expression was frequently lost, but MHC-II expression was maintained. CD4+ T cells highly infiltrated the tumor microenvironment of MHC-II–expressing cHL, regardless of MHC-I expression status. Consequently, CD4+ T-cell, but not CD8+ T-cell, infiltration was a good prognostic factor in cHL, and PD-1 blockade showed antitumor efficacy against MHC-II–expressing cHL associated with CD4+ T-cell infiltration. Murine lymphoma and solid tumor models revealed the critical role of antitumor effects mediated by CD4+ T cells: an anti-PD-1 monoclonal antibody exerted antitumor effects on MHC-I−MHC-II+ tumors but not on MHC-I−MHC-II− tumors, in a cytotoxic CD4+ T-cell–dependent manner. Furthermore, LAG-3, which reportedly binds to MHC-II, was highly expressed by tumor-infiltrating CD4+ T cells in MHC-II–expressing tumors. Therefore, the combination of LAG-3 blockade with PD-1 blockade showed a far stronger antitumor immunity compared with either treatment alone. We propose that PD-1 blockade therapies have antitumor effects on MHC-II–expressing tumors such as cHL that are mediated by cytotoxic CD4+ T cells and that LAG-3 could be a candidate for combination therapy with PD-1 blockade.

scholarly journals Adrenal Steroids Modulate the Immune Response during Brucella abortus Infection by a Mechanism That Depends on the Regulation of Cytokine Production

2015 ◽  
Vol 83 (5) ◽  
pp. 1973-1982 ◽  
Author(s):  
María Virginia Gentilini ◽  
Lis Noelia Velásquez ◽  
Paula Barrionuevo ◽  
Paula Constanza Arriola Benitez ◽  
Guillermo Hernán Giambartolomei ◽  
...  
Keyword(s):  
Immune Response ◽  
Clinical Signs ◽  
Human Brucellosis ◽  
Adrenal Steroids ◽  
Class I Mhc ◽  
Mhc I ◽  
Content Type ◽  
Mhc Ii ◽  
Ifn Γ ◽  
Dhea Treatment

Human brucellosis is a protean disease with a diversity of clinical signs and symptoms resulting from infection withBrucellaspecies. Recent reports suggest a cross-regulation between adrenal steroids (cortisol and dehydroepiandrosterone [DHEA]) and the immune system. Monocytes and macrophages are the main replication niche forBrucella. Therefore, we investigated the role of adrenal hormones on the modulation of the immune response mediated by macrophages inB. abortusinfection. Cortisol treatment duringB. abortusinfection significantly inhibits cytokine, chemokine, and MMP-9 secretion. In contrast, DHEA treatment had no effect. However, DHEA treatment increases the expression of costimulatory molecules (CD40, CD86), the adhesion molecule CD54, and major histocompatibility complex class I (MHC-I) and MHC-II expression on the surface ofB. abortus-infected monocytes. It is known thatB. abortusinfection inhibits MHC-I and MHC-II expression induced by gamma interferon (IFN-γ) treatment. DHEA reversesB. abortusdownmodulation of the MHC-I and -II expression induced by IFN-γ. Taken together, our data indicate that DHEA immune intervention may positively affect monocyte activity duringB. abortusinfection.

scholarly journals Brd4 Regulates the Homeostasis of CD8+ T-Lymphocytes and Their Proliferation in Response to Antigen Stimulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhilin Peng ◽  
Yiwen Zhang ◽  
Xiancai Ma ◽  
Mo Zhou ◽  
Shiyu Wu ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
T Cell Response ◽  
Cell Immune Response ◽  
Type I ◽  
T Cell Homeostasis ◽  
Cell Homeostasis ◽  
Antigen Stimulation

CD8+ T cells are major components of adaptive immunity and confer robust protective cellular immunity, which requires adequate T-cell numbers, targeted migration, and efficient T-cell proliferation. Altered CD8+ T-cell homeostasis and impaired proliferation result in dysfunctional immune response to infection or tumorigenesis. However, intrinsic factors controlling CD8+ T-cell homeostasis and immunity remain largely elusive. Here, we demonstrate the prominent role of Brd4 on CD8+ T cell homeostasis and immune response. By upregulating Myc and GLUT1 expression, Brd4 facilitates glucose uptake and energy production in mitochondria, subsequently supporting naïve CD8+ T-cell survival. Besides, Brd4 promotes the trafficking of naïve CD8+ T cells partially through maintaining the expression of homing receptors (CD62L and LFA-1). Furthermore, Brd4 is required for CD8+ T cell response to antigen stimulation, as Brd4 deficiency leads to a severe defect in clonal expansion and terminal differentiation by decreasing glycolysis. Importantly, as JQ1, a pan-BRD inhibitor, severely dampens CD8+ T-cell immune response, its usage as an anti-tumor agent or latency-reversing agent for human immunodeficiency virus type I (HIV-1) should be more cautious. Collectively, our study identifies a previously-unexpected role of Brd4 in the metabolic regulation of CD8+ T cell-mediated immune surveillance and also provides a potential immunomodulation target.

scholarly journals Revealing the role of CD4+ T cells in viral immunity

2012 ◽  
Vol 209 (8) ◽  
pp. 1391-1395 ◽  
Author(s):  
Andrea J. Sant ◽  
Andrew McMichael
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cd4 T Cells ◽  
Adaptive Immune Response ◽  
Neutralizing Antibody ◽  
Viral Immunity ◽  
Antigen Specificity ◽  
Viral Pathogens ◽  
Adaptive Immune

Protective immunity to chronic and acute viral infection relies on both the innate and adaptive immune response. Although neutralizing antibody production by B cells and cytotoxic activity of CD8+ T cells are well-accepted components of the adaptive immune response to viruses, identification of the specific role of CD4+ T cells in protection has been more challenging to establish. Delineating the contribution of CD4+ T cells has been complicated by their functional heterogeneity, breadth in antigen specificity, transient appearance in circulation, and sequestration in tissue sites of infection. In this minireview, we discuss recent progress in identifying the multiple roles of CD4+ T cells in orchestrating and mediating the immune responses against viral pathogens. We highlight several recent reports, including one published in this issue, that have employed comprehensive and sophisticated approaches to provide new evidence for CD4+ T cells as direct effectors in antiviral immunity.

scholarly journals CD8+γδ T Cells Are More Frequent in CMV Seropositive Bone Marrow Grafts and Display Phenotype of an Adaptive Immune Response

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Ahmed Gaballa ◽  
Lucas C. M. Arruda ◽  
Emelie Rådestad ◽  
Michael Uhlin
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Gene Segment ◽  
Adaptive Immune Response ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Adaptive Immune

The role of gamma delta (γδ) T cells in human cytomegalovirus (HCMV) immune surveillance has been the focus of research interest for years. Recent reports have shown a substantial clonal proliferation of γδ T cells in response to HCMV, shedding light on the adaptive immune response of γδ T cells. Nevertheless, most efforts have focused on Vδ2negγδ T cell subset while less attention has been given to investigate other less common γδ T cell subsets. In this regard, a distinct subpopulation of γδ T cells that expresses the CD8 coreceptor (CD8+γδ T cells) has not been thoroughly explored. Whether it is implicated in HCMV response and its ability to generate adaptive response has not been thoroughly investigated. In this study, we combined flow cytometry and immune sequencing of the TCR γ-chain (TRG) to analyze in-depth bone marrow (BM) graft γδ T cells from CMV seropositive (CMV+) and CMV seronegative (CMV-) donors. We showed that the frequency of CD8+γδ T cells was significantly higher in CMV+ grafts compared to CMV- grafts (P<0.001). Further characterization revealed that CD8+γδ T cells from CMV+ grafts express Vγ9- and preferentially differentiated from a naive to terminal effector memory phenotype (CD27low/-CD45RO-). In line with these findings, TRG immune sequencing revealed clonal focusing and reduced usage of the Vγ9/JP gene segment in a CMV+ graft. Furthermore, CD8+γδ T cells showed an enhanced response to TCR/CD3 and cytokine stimulation in contrast to CD8-γδ T cells. We conclude that γδ T cells in BM grafts are reshaped by donor CMV serostatus and highlight the potential adaptive role of CD8+γδ T cells in HCMV immune response.

scholarly journals Adaptive Immunity: The Role of Toll-Like Receptors

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yamaguchi R ◽  
◽  
Sakamoto A ◽  
Yamaguchi R ◽  
Haraguchi M ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Autoimmune Diseases ◽  
Adaptive Immunity ◽  
Th17 Cells ◽  
Adaptive Immune Response ◽  
Toll Like Receptors ◽  
Adaptive Immune ◽  
Interleukin 23

The central mediators of the adaptive immune response are T cells. The clonal expansion of T cells required for adaptive immunity results from the innate immune response, which is triggered by the stimulation of Toll-Like Receptors (TLRs). The adaptive immune response can cause autoimmune diseases, and Th17 cells are known to contribute to several autoimmune diseases. Pathogenic Th17 cells are induced by Interleukin 23 (IL-23) and IL-1Β. Resiquimod (a TLR7/8 agonist) significantly enhances IL-23 production by human macrophages, and lipopolysaccharide (a TLR4 agonist) slightly enhances it. Interestingly, IL-23 levels are significantly attenuated after sequential stimulation with lipopolysaccharide and resiquimod, indicating cross-talk between the TLR4 and TLR7/8 signaling pathways. In this review, we discuss the pivotal role of TLRs in triggering innate immunity and inducing adaptive immunity, leading to autoimmune diseases.

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