scholarly journals CD8+T Cell-Mediated Immunity duringTrypanosoma cruziInfection: A Path for Vaccine Development?

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Fernando dos Santos Virgilio ◽  
Camila Pontes ◽  
Mariana Ribeiro Dominguez ◽  
Jonatan Ersching ◽  
Mauricio Martins Rodrigues ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Disease Transmission ◽  
Vaccine Development ◽  
Experimental Studies ◽  
Chronic Phase ◽  
Protozoan Parasite ◽  
Active Role ◽  
Cell Mediated Immunity ◽  
High Proliferative Activity

MHC-restrictedCD8+T cells are important during infection with the intracellular protozoan parasiteTrypanosoma cruzi, the causative agent of Chagas disease. Experimental studies performed in the past 25 years have elucidated a number of features related to the immune response mediated by these T cells, which are important for establishing the parasite/host equilibrium leading to chronic infection.CD8+T cells are specific for highly immunodominant antigens expressed by members of thetrans-sialidase family. After infection, their activation is delayed, and the cells display a high proliferative activity associated with high apoptotic rates. Although they participate in parasite control and elimination, they are unable to clear the infection due to their low fitness, allowing the parasite to establish the chronic phase when these cells then play an active role in the induction of heart immunopathology. Vaccination with a number of subunit recombinant vaccines aimed at eliciting specificCD8+T cells can reverse this path, thereby generating a productive immune response that will lead to the control of infection, reduction of symptoms, and reduction of disease transmission. Due to these attributes, activation ofCD8+T lymphocytes may constitute a path for the development of a veterinarian or human vaccine.

Human Cytomegalorivus Induces Actin Cytoskeleton Abnormity in Infected Dendritic Cells with the Consequence of Depressed Immunological Functions.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5366-5366
Author(s):  
Mao-fang Lin ◽  
Guang-sheng Zhao
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Actin Cytoskeleton ◽  
Mrna Level ◽  
Microscopic Analysis ◽  
Active Role ◽  
Brdu Incorporation ◽  
Immune Recognition ◽  
Early Antigen

Abstract Dendritic cells(DCs) are considered the most potent antigen presenting cells(APC) and accordingly play a crucial role in initiating and maintaining the adaptive immune response against viruses. The DCs actin cytoskeleton plays an active role in the immunological synapse and may explain the unique ability of DCs to activate resting T cells. Human cytomegalorivus (HCMV) is an important human pathogen that has long been known to induce or enhance immunosuppression in patients. The HCMV-associated defect in the cellular immune response has been attributed to alterations in the function of T lymphocytes and have an important influence upon stem cell transplantation outcome. However, the precise molecular mechanism by which HCMV alters the host immune response such as the effect on DCs is a longstanding enigma and remains to defined. In this study, we investigated the susceptibility of DCs at different stage to HCMV infection and the functional consequence thereof. At the immature stage of monocyte-derived DCs, viral immediately early antigen (IEA) mRNA and early antigen (EA)protein could be detected by RT-PCR and immunoflourescence microscopic analysis, respectively. The relative expression of IE mRNA in mature DCs was lower than immature DCs at 12h after infecion, 0.102±0.020 and 0.862±0.124, respectively (P<0.05). EA, primarily localized in nucleus, could be found in (62.32±14.20)% immature and (10.78±3.04)% immature DCs at 24h, repectively (P<0.01). pp65(CMV late antigen) positive cells in immature and mature DCs at 72h were (4.24±0.38)% and (0.82±0.13)%. However, after inducing maturation by LPS, these DCs showed no evidence of active infection. In infected DCs,β-actin got a significant and gradual decreasing of mRNA level. Compared with uninfected group, the expression of β-actin protein decreased to (61.8±17.4)% at 96h after infection. while the ratio of globular actin (G-actin) and fibrous actin (F-actin) increased to (201.3±42.7)% at 24h. HCMV infected immature DCs were significantly impaired in their ability to endocytose FITC-labeled dextran particles detected by flow cytometry, while uninfected DCs exhibited a high endocytic capacity(approximately 40 to 50% reduction). An impaired ability of HCMV infected DCs to mature in response to LPS could be observed. Both MHC class I and II molecules on the surface of DCs were significantly downregulated after inducing maturation by LPS compared with uninfected cells,(92.0±3.9)% versus (46.4±5.0)% for MHC I molecule and (91.8±5.3)% versus (54.3±5.7)% for MHC II molecule(both P<0.05). In contrast, the costimulatory molecules CD80,CD86 were slightly upregulated,(62.4±8.3)% versus (73.8±7.4)% for CD80 and (67.3±7.6)% versus (77.8±8.9)% for CD86. The proliferative response of T cells was drastically reduced detected by BrdU incorporation, however, this reduced capacity to stimulate alloreactive T cells could be partly restored by adding actin aggregation activator PMA(2μmol/L). In summary, we propose that the infection of immature DCs allows HCMV to evade immune recognition and T cells attack. The actin cytoskeleton abnormity in infected cells may play a pivotal role in HCMV-triggered immunosuppression.

scholarly journals PROTEIN REKOMBINAN 38 KDA MYCOBAKTERIUM TUBERKULOSIS DAPAT MENGIMBAS PEMBUATAN INTERLEUKIN-2 DAN INTERFERON-γ LIMFOSIT T DI KULTUR SEL MONONUKLEAR DARAH TEPI

2018 ◽  
Vol 22 (2) ◽  
pp. 151
Author(s):  
Maimun Z Arthamin ◽  
Singgih Pujo Wahono ◽  
Antiek Primardianti ◽  
Ati Rastini ◽  
Tri Wahju Astuti ◽  
...  
Keyword(s):  
Immune Response ◽  
T Lymphocytes ◽  
Recombinant Protein ◽  
Vaccine Development ◽  
Interleukin 2 ◽  
Development Program ◽  
In Vitro Study ◽  
Cell Mediated Immunity ◽  
Ifn Γ

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (M.tb) and is one of the significant mortality causes WHO (2012). Theprimary immune response in TB pathogenesis is Cell Mediated Immunity (CMI), roled by T lymphocytes. Interleukin-2 (IL-2) is a growthfactor for T lymphocytes. Gamma Interferon is the key cytokine in M.tb infection control, synthezised by T lymphocytes. An effectivevaccination strategy is achieved by giving vaccine which is able to stimulate T lymphocytes in synthezising cytokines. The 38 kDa M.tbprotein is potential in the vaccine development program, because it has specific epitopes for T lymphocytes. The aim of this study was toknow how to determine that the 38 kDa recombinant protein of M.tb Malang strain could induce cellular immune response by IL-2 andIFN-γ synthezised by T lymphocytes. The study was carried out by an experimental in vitro study on PBMC from healthy endemic subjects,those having TB contact, and the TB patients themselves. PBMC from subjects was cultured with 38 kDa recombinant protein of M.tbMalang strain, with PPD and without any protein. The analysis of IL-2 and IFN-γ used flowcytometry. The result showed that the highestpercentage of IL-2 was found in the culture with 38 kDa recombinant protein of M.tb Malang strain, in healthy endemic (p=0.000)and in those who had TB contact (p=0.000). the highest percentage of IFN-γ was found in the culture with 38 kDa recombinant proteinof M.tb Malang strain, in healthy endemic (p=0.007) and those who had TB contact (p = 0.105). The 38 kDa recombinant proteinof M.tb Malang strain was able to induce IL-2 and IFN-γ synthezised by TCD3+ lymphocytes from healthy endemic subjects and thosewho had TB contact.

Cellular side of acquired immunity (T cells)

2013 ◽  
Author(s):  
Assia Eljaafari ◽  
Pierre Miossec
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune System ◽  
Disease Process ◽  
T Cell Response ◽  
Th2 Cells ◽  
Cell Mediated Immunity ◽  
Immune Effector ◽  
Effector Cells ◽  
Th22 Cells

The adaptive T-cell response represents the most sophisticated component of the immune response. Foreign invaders are recognized first by cells of the innate immune system. This leads to a rapid and non-specific inflammatory response, followed by induction of the adaptive and specific immune response. Different adaptive responses can be promoted, depending on the predominant effector cells that are involved, which themselves depend on the microbial/antigen stimuli. As examples, Th1 cells contribute to cell-mediated immunity against intracellular pathogens, Th2 cells protect against parasites, and Th17 cells act against extracellular bacteria and fungi that are not cleared by Th1 and Th2 cells. Among the new subsets, Th22 cells protect against disruption of epithelial layers secondary to invading pathogens. Finally these effector subsets are regulated by regulatory T cells. These T helper subsets counteract each other to maintain the homeostasis of the immune system, but this balance can be easily disrupted, leading to chronic inflammation or autoimmune diseases. The challenge is to detect early changes in this balance, prior to its clinical expression. New molecular tools such as microarrays could be used to determine the predominant profile of the immune effector cells involved in a disease process. Such understanding should provide better therapeutic tools to counteract deregulated effector cells.

scholarly journals Chimeric Vaccines Designed by Immunoinformatics-Activated Polyfunctional and Memory T Cells That Trigger Protection against Experimental Visceral Leishmaniasis

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 252 ◽  
Author(s):  
Rory Cristiane Fortes De Brito ◽  
Jeronimo Conceição Ruiz ◽  
Jamille Mirelle de Oliveira Cardoso ◽  
Thais Lopes Valentim Di Paschoale Ostolin ◽  
Levi Eduardo Soares Reis ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Visceral Leishmaniasis ◽  
Vaccine Development ◽  
Memory T Cells ◽  
Parasite Burden ◽  
Effector Memory ◽  
Potential Candidate ◽  
Protective Mechanisms ◽  
Strong Immune Response

Many vaccine candidates against visceral leishmaniasis (VL) have been proposed; however, to date, none of them have been efficacious for the human or canine disease. On this basis, the design of leishmaniasis vaccines has been constantly changing, and the use of approaches to select specific epitopes seems to be crucial in this scenario. The ability to predict T cell-specific epitopes makes immunoinformatics an even more necessary approach, as in VL an efficient immune response against the parasite is triggered by T lymphocytes in response to Leishmania spp. immunogenic antigens. Moreover, the success of vaccines depends on the capacity to generate long-lasting memory and polyfunctional cells that are able to eliminate the parasite. In this sense, our study used a combination of different approaches to develop potential chimera candidate vaccines against VL. The first point was to identify the most immunogenic epitopes of Leishmania infantum proteins and construct chimeras composed of Major histocompatibility complex (MHC) class I and II epitopes. For this, we used immunoinformatics features. Following this, we validated these chimeras in a murine model in a thorough memory study and multifunctionality of T cells that contribute to a better elucidation of the immunological protective mechanisms of polyepitope vaccines (chimera A and B) using multicolor flow cytometry. Our results showed that in silico-designed chimeras can elicit polyfunctional T cells producing T helper (Th)1 cytokines, a strong immune response against Leishmania antigen, and the generation of central and effector memory T cells in the spleen cells of vaccinated animals that was able to reduce the parasite burden in this organ. These findings contribute two potential candidate vaccines against VL that can be used in further studies, and help in this complex field of vaccine development against this challenging parasite.

scholarly journals Cell-Mediated Immune Response during Primary Chlamydia pneumoniae Infection

2000 ◽  
Vol 68 (12) ◽  
pp. 7156-7158 ◽  
Author(s):  
S. Halme ◽  
J. Latvala ◽  
R. Karttunen ◽  
I. Palatsi ◽  
P. Saikku ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Interferon Gamma ◽  
Early Phase ◽  
Lymphocyte Proliferation ◽  
Chlamydia Pneumoniae ◽  
Cell Mediated Immunity ◽  
Specific Cell ◽  
Cell Mediated Immune Response

ABSTRACT The development of Chlamydia pneumoniae-specific cell-mediated immunity was studied during a primary C. pneumoniae infection. The immune response was detected as positive lymphocyte proliferation and secretion of interferon gamma.C. pneumoniae-induced activation of both CD4+and CD8+ T cells was detected in the early phase of infection, but activation of only CD4+ T cells was detected in the later stage.

scholarly journals Structures of the MHC-I molecule BF2*1501 disclose the preferred presentation of an H5N1 virus-derived epitope

2020 ◽  
Vol 295 (16) ◽  
pp. 5292-5306 ◽  
Author(s):  
Xiaoying Li ◽  
Lijie Zhang ◽  
Yanjie Liu ◽  
Lizhen Ma ◽  
Nianzhi Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Molecular Mechanisms ◽  
Vaccine Development ◽  
Highly Pathogenic Avian Influenza ◽  
Cell Mediated Immunity ◽  
Highly Pathogenic ◽  
Mhc I ◽  
Specific Pathogen ◽  
Pathogenic Avian Influenza Virus

Lethal infections by strains of the highly-pathogenic avian influenza virus (HPAIV) H5N1 pose serious threats to both the poultry industry and public health worldwide. A lack of confirmed HPAIV epitopes recognized by cytotoxic T lymphocytes (CTLs) has hindered the utilization of CD8+ T-cell–mediated immunity and has precluded the development of effectively diversified epitope-based vaccination approaches. In particular, an HPAIV H5N1 CTL-recognized epitope based on the peptide MHC-I–β2m (pMHC-I) complex has not yet been designed. Here, screening a collection of selected peptides of several HPAIV strains against a specific pathogen-free pMHC-I (pBF2*1501), we identified a highly-conserved HPAIV H5N1 CTL epitope, named HPAIV–PA123–130. We determined the structure of the BF2*1501–PA123–130 complex at 2.1 Å resolution to elucidate the molecular mechanisms of a preferential presentation of the highly-conserved PA123–130 epitope in the chicken B15 lineage. Conformational characteristics of the PA123–130 epitope with a protruding Tyr-7 residue indicated that this epitope has great potential to be recognized by specific TCRs. Moreover, significantly increased numbers of CD8+ T cells specific for the HPAIV–PA123–130 epitope in peptide-immunized chickens indicated that a repertoire of CD8+ T cells can specifically respond to this epitope. We anticipate that the identification and structural characterization of the PA123–130 epitope reported here could enable further studies of CTL immunity against HPAIV H5N1. Such studies may aid in the development of vaccine development strategies using well-conserved internal viral antigens in chickens.

scholarly journals Vaccine-induced protective immunity against coxiella burnetii

2019 ◽  
Author(s):  
◽  
Lindsey Elizabeth Ledbetter
Keyword(s):  
T Cells ◽  
Coxiella Burnetii ◽  
Protective Immunity ◽  
Vaccine Development ◽  
Q Fever ◽  
Therapeutic Vaccine ◽  
T Cell Subsets ◽  
Cell Mediated Immunity ◽  
Vaccine Protection ◽  
Vaccine Immunity

Coxiella burnetii is an obligate intracellular Gram-negative bacterial pathogen and the causative agent of human Q fever. This disease presents acutely as a flu-like illness, although it can escalate to a chronic and often fatal disease when left untreated. Considering no FDA-approved vaccine exists, the creation of a safe and effective vaccine remains an important public health goal. A formalin-inactivated C. burnetii Nine Mile strain phase I whole-cell vaccine generates protective immunity in a mouse model of experimental Q fever, although the mechanisms of protection remain unclear. Chapter 3 details my work establishing an early vaccine protection model and elucidating the cellular immune response which elicits early protection. The early time point at which PIV protects has implications for its use as a therapeutic vaccine. Furthermore, the innate-driven mechanisms by which it protects can be exploited for an improved Q fever vaccine. The importance of T cells in vaccine immunity against C. burnetii is well supported, however, multiple questions remain. It is unclear how CD4+ or CD8+ T cells contribute to vaccine protection, and the role of specific CD4+ T cell subsets is unknown. IFN-[theta] is critical for primary defense against C. burnetii, though its importance in vaccine immunity is undetermined. Chapter 4 describes my work aimed at filling these knowledge gaps. Vaccine development efforts have largely focused on the generation of antibodies as a correlate of protection. It has become clear that targeting T cells is more critical to vaccine protection and a better understanding of the mechanisms of cell-mediated immunity will inform future Q fever vaccine development.

scholarly journals Recent Progress in Vaccine Development againstLeishmaniaSpecies Infections

1999 ◽  
Vol 10 (suppl c) ◽  
pp. 9C-15C ◽  
Author(s):  
Barbara Papadopoulou ◽  
Martin Olivier ◽  
Marc Ouellette
Keyword(s):  
T Cell ◽  
Cellular Immunity ◽  
Recent Progress ◽  
Vaccine Development ◽  
Dna Vaccines ◽  
Protozoan Parasite ◽  
Cell Mediated Immunity ◽  
Subunit Vaccines ◽  
Vaccination Strategies ◽  
Parasite Leishmania

The understanding of the immunobiology of infections caused by the protozoan parasite leishmania is now extensive and has pinpointed the importance of T cell-mediated immunity. Several vaccination strategies using either killed parasites, subunit vaccines, DNA vaccines or live attenuated strains have been used successfully with and without adjuvants to induce cellular immunity and protect against leishmania infections. The most recent progress in leishmania vaccine development is described.

scholarly journals Magnitude and Dynamics of the T-Cell Response to SARS-CoV-2 Infection at Both Individual and Population Levels

2020 ◽  
Author(s):  
Thomas M Snyder ◽  
Rachel M Gittelman ◽  
Mark Klinger ◽  
Damon H May ◽  
Edward J Osborne ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Vaccine Development ◽  
Human Leukocyte ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Clinical Diagnostics ◽  
Cell Repertoire

T cells are involved in the early identification and clearance of viral infections and also support the development of antibodies by B cells. This central role for T cells makes them a desirable target for assessing the immune response to SARS-CoV-2 infection. Here, we combined two high-throughput immune profiling methods to create a quantitative picture of the T-cell response to SARS-CoV-2. First, at the individual level, we deeply characterized 3 acutely infected and 58 recovered COVID-19 subjects by experimentally mapping their CD8 T-cell response through antigen stimulation to 545 Human Leukocyte Antigen (HLA) class I presented viral peptides (class II data in a forthcoming study). Then, at the population level, we performed T-cell repertoire sequencing on 1,815 samples (from 1,521 COVID-19 subjects) as well as 3,500 controls to identify shared "public" T-cell receptors (TCRs) associated with SARS-CoV-2 infection from both CD8 and CD4 T cells. Collectively, our data reveal that CD8 T-cell responses are often driven by a few immunodominant, HLA-restricted epitopes. As expected, the T-cell response to SARS-CoV-2 peaks about one to two weeks after infection and is detectable for at least several months after recovery. As an application of these data, we trained a classifier to diagnose SARS-CoV-2 infection based solely on TCR sequencing from blood samples, and observed, at 99.8% specificity, high early sensitivity soon after diagnosis (Day 3-7 = 85.1% [95% CI = 79.9-89.7]; Day 8-14 = 94.8% [90.7-98.4]) as well as lasting sensitivity after recovery (Day 29+/convalescent = 95.4% [92.1-98.3]). These results demonstrate an approach to reliably assess the adaptive immune response both soon after viral antigenic exposure (before antibodies are typically detectable) as well as at later time points. This blood-based molecular approach to characterizing the cellular immune response has applications in clinical diagnostics as well as in vaccine development and monitoring.

Effect of Costimulation and the Microenvironment on Antigen Presentation by Leukemic Cells

Blood ◽  
1999 ◽  
Vol 94 (10) ◽  
pp. 3479-3490 ◽  
Author(s):  
A.G.S. Buggins ◽  
N. Lea ◽  
J. Gäken ◽  
D. Darling ◽  
F. Farzaneh ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Tumor Cells ◽  
Costimulatory Molecule ◽  
Leukemic Cells ◽  
Cell Mediated Immunity ◽  
Cell Recognition ◽  
T Cell Recognition ◽  
Th1 Cytokines

Costimulatory signals supplied by genetically modified tumor cells can enable T-cell recognition of tumor-associated antigens that were previously silent when presented by unmodified tumor cells. Although the mechanism of the CD80/CD28 costimulation has been studied extensively in the normal T-cell/antigen-presenting cell (APC) interactions, it is unclear how expression of CD80 by tumor cells mediates its effect. We demonstrate here that optimal CD80 expression on a leukemic cell enhances T-cell recognition of alloantigen primarily by lowering the level of T-cell receptor (TCR) stimulation required for activation. CD80 expression by leukemic cells leads to increased survival of activated T cells by inducing upregulation of the antiapoptotic protein BCL-2, but not BCL-XL. The cytokine microenvironment in which T cells are activated is crucial in determining their differentiation and consequently the nature of the immune response generated. Many tumor cells produce immunosuppressive cytokines that may not favor the induction of cell-mediated immunity. In this study, the presence of CD80 on leukemic cells increased T-cell activation in vitro, but this did not result in the production of Th1 cytokines. We show that this is due to a leukemia-derived soluble factor that inhibits the production of Th1 cytokines. Optimal expression of a costimulatory molecule, therefore, enhances the ability of leukemic cells to present antigen by amplifying TCR signals, but the microenvironment generated by leukemic cells may suppress the immune response required for their eradication. Thus, strategies aimed at inducing antileukemic immunity by providing leukemic cells with costimulatory functions must ensure the presence of an appropriate microenvironment.

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