scholarly journals Lung memory T-cell response in mice following intranasal immunization with influenza vector expressing mycobacterial proteins

2020 ◽  
Vol 10 (3) ◽  
pp. 506-514
Author(s):  
A.-P. S. Shurygina ◽  
N. V. Zabolotnykh ◽  
T. I. Vinogradova ◽  
K. A. Vasilyev ◽  
Zh. V. Buzitskaya ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Lymphocytes ◽  
Vaccine Candidate ◽  
Memory T Cells ◽  
Bcg Vaccine ◽  
Tuberculosis Infection ◽  
Effector Memory ◽  
Intranasal Immunization ◽  
Boost Vaccination

Improving specific prevention of tuberculosis continues to be a top priority in phthisiology. “Prime-boost” vaccination schemes aim to maintain adequate levels of specific immunity while forming long-term protection. They are based on sequential use of BCG vaccine and new vaccine candidates expressing protective mycobacterial proteins. The development of new tuberculosis prevention approaches requires an understanding of how the anti-tuberculosis immune response forms and which mechanisms provide TB protection. Since tuberculosis is an airborne infection, vaccine effectiveness largely depends on mucosal immunity based on the formation of long-lived, functionally-active memory T-lymphocytes in the respiratory tract. We have previously shown that the influenza vector expressing ESAT-6 and Ag85A mycobacterial proteins (Flu/ESAT-6_Ag85A) in vaccination scheme of intranasal boost immunization resulted in significant increase of BCG's protective effect according to key indicators aggregate data in experimental tuberculosis infection. The aim of this work was to study the effect of intranasal immunization with the Flu/ESAT-6_Ag85A influenza vector on the formation of antigen-specific central and effector memory T cells and the cytokine-producing activity of effector T cells (TEM) in BCG standard and “BCG prime — influenza vector boost” vaccination schemes in mice. Intranasal immunization with the influenza vector has been shown to increase the proportion of antigen-specific CD4+ central memory T cells (TCM) in the pool of activated lymphocytes of lung and spleen reaching significant differences from the BCG group in the percentage of spleen CD4+ TCM (p < 0.01). In contrast to BCG, vaccination with the studied vaccine candidate was accompanied by accumulation of highly differentiated CD8 effector cells in lung, the target organ during tuberculosis infection. Comparative evaluation of the cell-mediated, post-vaccine immune response after immunization with influenzavector-based vaccine candidate (intranasal/mucosal) or BCG vaccine (subcutaneous) showed advantages in the mucosal group: in formation of functionally active subpopulations of effector CD4 and CD8 T lymphocytes (CD44highCD62Llow) in lungs secreting IL-2 as well as polyfunctional cells capable of coproducing two cytokines (IFNγ/TNFα or IFNγ/IL-2) or three cytokines (IFNγ/TNFα/IL-2). Due to their more pronounced effector function, polyfunctional T-lymphocytes can be considered to be potential immunological markers of protective immunity in tuberculosis.

scholarly journals Evaluation of the Immunogenicity of Mycobacterium bovis BCG Delivered by Aerosol to the Lungs of Macaques

2015 ◽  
Vol 22 (9) ◽  
pp. 992-1003 ◽  
Author(s):  
A. D. White ◽  
C. Sarfas ◽  
K. West ◽  
L. S. Sibley ◽  
A. S. Wareham ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Mycobacterium Bovis ◽  
Cd8 T Cells ◽  
Bcg Vaccine ◽  
Effector Memory ◽  
Dependent Manner ◽  
Aerosol Delivery ◽  
Memory Phenotype ◽  
Bcg Vaccination

ABSTRACTNine million cases of tuberculosis (TB) were reported in 2013, with a further 1.5 million deaths attributed to the disease. When delivered as an intradermal (i.d.) injection, theMycobacterium bovisBCG vaccine provides limited protection, whereas aerosol delivery has been shown to enhance efficacy in experimental models. In this study, we used the rhesus macaque model to characterize the mucosal and systemic immune response induced by aerosol-delivered BCG vaccine. Aerosol delivery of BCG induced both Th1 and Th17 cytokine responses. Polyfunctional CD4 T cells were detected in bronchoalveolar lavage (BAL) fluid and peripheral blood mononuclear cells (PBMCs) 8 weeks following vaccination in a dose-dependent manner. A similar trend was seen in peripheral gamma interferon (IFN-γ) spot-forming units measured by enzyme-linked immunosorbent spot (ELISpot) assay and serum anti-purified protein derivative (PPD) IgG levels. CD8 T cells predominantly expressed cytokines individually, with pronounced tumor necrosis factor alpha (TNF-α) production by BAL fluid cells. T-cell memory phenotype analysis revealed that CD4 and CD8 populations isolated from BAL fluid samples were polarized toward an effector memory phenotype, whereas the frequencies of peripheral central memory T cells increased significantly and remained elevated following aerosol vaccination. Expression patterns of the α4β1 integrin lung homing markers remained consistently high on CD4 and CD8 T cells isolated from BAL fluid and varied on peripheral T cells. This characterization of aerosol BCG vaccination highlights features of the resulting mycobacterium-specific immune response that may contribute to the enhanced protection previously reported in aerosol BCG vaccination studies and will inform future studies involving vaccines delivered to the mucosal surfaces of the lung.

scholarly journals Contribution of Resident Memory CD8+ T Cells to Protective Immunity Against Respiratory Syncytial Virus and Their Impact on Vaccine Design

Pathogens ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 147 ◽  
Author(s):  
Retamal-Díaz ◽  
Covián ◽  
Pacheco ◽  
Castiglione-Matamala ◽  
Bueno ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Respiratory Syncytial Virus ◽  
Viral Infections ◽  
Memory T Cells ◽  
Effector Memory ◽  
Memory Cells ◽  
Effective Immune Response ◽  
Syncytial Virus ◽  
Tract Infections

Worldwide, human respiratory syncytial virus (RSV) is the most common etiological agent for acute lower respiratory tract infections (ALRI). RSV-ALRI is the major cause of hospital admissions in young children, and it can cause in-hospital deaths in children younger than six months old. Therefore, RSV remains one of the pathogens deemed most important for the generation of a vaccine. On the other hand, the effectiveness of a vaccine depends on the development of immunological memory against the pathogenic agent of interest. This memory is achieved by long-lived memory T cells, based on the establishment of an effective immune response to viral infections when subsequent exposures to the pathogen take place. Memory T cells can be classified into three subsets according to their expression of lymphoid homing receptors: central memory cells (TCM), effector memory cells (TEM) and resident memory T cells (TRM). The latter subset consists of cells that are permanently found in non-lymphoid tissues and are capable of recognizing antigens and mounting an effective immune response at those sites. TRM cells activate both innate and adaptive immune responses, thus establishing a robust and rapid response characterized by the production of large amounts of effector molecules. TRM cells can also recognize antigenically unrelated pathogens and trigger an innate-like alarm with the recruitment of other immune cells. It is noteworthy that this rapid and effective immune response induced by TRM cells make these cells an interesting aim in the design of vaccination strategies in order to establish TRM cell populations to prevent respiratory infectious diseases. Here, we discuss the biogenesis of TRM cells, their contribution to the resolution of respiratory viral infections and the induction of TRM cells, which should be considered for the rational design of new vaccines against RSV.

scholarly journals Subsets of Memory Cytotoxic T Lymphocytes Elicited by Vaccination Influence the Efficiency of Secondary Expansion In Vivo

2004 ◽  
Vol 78 (1) ◽  
pp. 206-215 ◽  
Author(s):  
Michael S. Seaman ◽  
Fred W. Peyerl ◽  
Shawn S. Jackson ◽  
Michelle A. Lifton ◽  
Darci A. Gorgone ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Memory T Cells ◽  
Central Memory ◽  
Effector Memory ◽  
Interleukin 12 ◽  
Effector Cells ◽  
Memory Cytotoxic T Lymphocytes

ABSTRACT Vaccine-elicited cytotoxic T lymphocytes (CTL) should be long-lived memory cells that can rapidly expand in number following re-exposure to antigen. The present studies were initiated to analyze the ability of plasmid interleukin-12 (IL-12) to augment CTL responses in mice when delivered during the peak phase of an immune response elicited by a plasmid human immunodeficiency virus type 1 gp120 DNA vaccine. Delivery of plasmid IL-12 on day 10 postimmunization resulted in a robust expansion of gp120-specific CD8+ T cells, as measured by tetramer, gamma interferon ELISPOT, and functional-killing assays. Interestingly, this delayed administration of plasmid IL-12 had no significant effect on antigen-specific CD4+-T-cell and antibody responses. Phenotypic analyses suggested that administration of plasmid IL-12 near the time of the peak CTL response activated and expanded antigen-specific effector cells, preventing their loss through apoptosis. However, this IL-12-augmented population of gp120-specific CD8+ T cells did not efficiently expand following gp120 boost immunization, suggesting that these effector cells would be of little utility in expanding to contain a viral infection. Analyses of the phenotypic profile and anatomic distribution of the plasmid IL-12-augmented CTL population indicated that these lymphocytes were primarily effector memory rather than central memory T cells. These observations suggest that CTL-based vaccines should elicit central memory rather than effector memory T cells and illustrate the importance of monitoring the phenotype and functionality of vaccine-induced, antigen-specific CTL.

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 Rapid and stable mobilization of fully functional spike-specific CD8+ T cells preceding a mature humoral response after SARS-CoV-2 mRNA vaccination

2021 ◽  
Author(s):  
Robert Thimme ◽  
Valerie Oberhardt ◽  
Hendrik Luxenburger ◽  
Janine Kemming ◽  
Isabel Schulien ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Adaptive Immunity ◽  
Cd8 T Cells ◽  
Neutralizing Antibodies ◽  
Memory T Cells ◽  
Natural Infection ◽  
Cd8 T Cell ◽  
Effector Memory ◽  
Boost Vaccination

Abstract SARS-CoV-2 spike mRNA vaccines mediate protection from severe disease as early as 10 days post prime vaccination, when specific antibodies are hardly detectable and still lack neutralizing activity. Vaccine-induced T cells, especially CD8+ T cells, may thus be the main mediators of protection at this early stage. The details of antigen-specific CD8+ T cell induction after prime/boost vaccination, their comparison to naturally induced CD8+ T cell responses and their association with other arms of vaccine-induced adaptive immunity remain, however, incompletely understood. Here, we show on a single epitope level that both, a stable memory precursor pool of spike-specific CD8+ T cells and fully functional spike-specific effector CD8+ T cell populations, are vigorously mobilized as early as one week after prime vaccination when CD4+ T cell and spike-specific antibody responses are still weak and neutralizing antibodies are lacking. Boost vaccination after 3 weeks induced a full-fledged recall expansion generating highly differentiated CD8+ effector T cells, however, neither the functional capacity nor the memory precursor T cell pool was affected. Compared to natural infection, vaccine-induced early memory T cells exhibited similar frequencies and functional capacities but a different subset distribution dominated by effector memory T cells at the expense of self-renewing and multipotent central memory T cells. Our results indicate that spike-specific CD8+ T cells may represent the major correlate of early protection after SARS-CoV-2 mRNA/bnt162b2 prime vaccination that precede other effector arms of vaccine-induced adaptive immunity and are stably maintained after boost vaccination.

Tumor-infiltrating lymphocytes in ipsilateral breast tumor recurrences predict prognosis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 546-546
Author(s):  
Axel Stenmark Tullberg ◽  
Emma Nimeus-Malmström ◽  
Fredrika Killander ◽  
Martin Sjöström ◽  
Henri A.J. Puttonen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
T Cells ◽  
Distant Metastasis ◽  
Breast Tumor ◽  
Memory T Cells ◽  
Effector Memory ◽  
Matched Pairs ◽  
Ipsilateral Breast ◽  
Gene Expression Analyses

546 Background: The antitumoral immune response is dynamic and changes with tumor progression. Previous studies show that immunohistochemical (IHC) assessment of TILs in local recurrences can predict prognosis. It is not clear how adjuvant radiotherapy (RT) can alter the local immune response or if gene expression analyses of TILs in recurrences can provide prognostic information. Methods: Matched biopsies from primary tumors and ipsilateral breast tumor recurrences (IBTRs) from the randomized SweBCG91RT trial were assessed for TILs. Analyses were performed using gene expression (86 matched pairs) and IHC assessment (126 matched pairs). Results: The median time to IBTR was 8.0 years among irradiated patients and 3.6 years among unirradiated patients. In the gene expression analyses, higher absolute values of CD8+ T cells, CD4+ effector memory and CD8+ effector memory T cells in the recurrence could significantly predict a decreased risk of subsequent distant metastasis. In addition, a net increase of these cells in the IBTR compared to the primary tumor was associated with a significantly lower risk of metastasis. TILs did not change significantly between the matched tumors for the whole group or among irradiated patients versus unirradiated patients in the gene expression or IHC analyses. Surprisingly, the group with unchanged TILs levels as measured by IHC had the lowest risk of metastasis while an increase or a decrease in TILs was significantly associated with an increased risk. Conclusions: Cytotoxic and memory T cells in the recurrence protect against subsequent distant metastasis although IHC measurement of TILs could not confirm these results. No significant differences in TILs infiltration between irradiated versus unirradiated patients could be determined in the recurrences. Further analyses including changes of subtypes between the primary tumor and the recurrence will be presented.

scholarly journals CONTENTS OF CD4+ AND CD8+ EFFECTOR MEMORY CELLS AND PROLIFERATIVE ACTIVITY OF T LYMPHOCYTES IN BRONCHIAL ASTHMA

2019 ◽  
Vol 21 (3) ◽  
pp. 503-516
Author(s):  
M. Sh. Barkovskaya ◽  
E. A. Blinova ◽  
L. V. Grishina ◽  
M. I. Leonova ◽  
V. M. Nepomniashchikch ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Bronchial Asthma ◽  
Proliferative Activity ◽  
Memory T Cells ◽  
Effector Memory ◽  
Memory Cells ◽  
Healthy Donors ◽  
Effector Memory Cells

Bronchial asthma is a chronic inflammatory disease of the respiratory tract. T-lymphocytes play a key role in pathogenesis of this allergic disease. The reduction in number of naïve T cells and the accumulation of memory T cells in bronchial asthma are accompanied by dysregulation of T lymphocyte function. In present study, we have investigated the contents of different T lymphocyte subpopulations in peripheral blood as well as in resting and PHA-stimulated cultures, along with their proliferative capacity in patients with bronchial asthma and healthy donors. The study included 10 patients with bronchial asthma (age 45.4±11.8 years). One-half of patients was in remission state, the others having been at the stage of clinical exacerbation. The group of donors was formed by healthy individuals matched by gender and age to the patients. Based on expression of cell surface markers CD45R0, CD62L and CD197 (CCR7), the CD4+ and CD8+T lymphocytes were divided into central (Tcm) and effector memory cells (Tem), naïve T lymphocytes (Tnaïve) and terminally differentiated effector cells (Temra) using flow cytometry technique. The proliferative activity of Tcm, Tem and Tnaïve was evaluated in response to PHA as a functional marker of T cells. We have found that the percentage of peripheral CD4+TemCD62L+ and CD8+TemCD62L+ cells in the patients with asthma exacerbation was significantly reduced, if compared to the donors. Following PHA stimulation, these differences in T cell subsets between the groups of patients and donors were not detectable. We performed a correlation analysis between the memory T cell contents and age of the subjects studied. It was shown that the relative amounts of CD4+ and CD8+ memory cells increased with age in asthmatics, but not in healthy donors. Analysis of mitogen-induced proliferation showed that Tcm and Tnaïve cells proliferated more actively than other subpopulations in both groups. Meanwhile, the proliferative activity of CD4+T lymphocytes and subsets of CD8+Tcm, CD4+Tcm and CD4+Tem62L was higher in the group of asthma patients in remission state than in the patients with exacerbating disease, and healthy donors. The revealed increase in the relative number of memory T cells with age suggests that these cells participate in development of bronchial asthma. Proliferative response of the studied subpopulations, which was comparable to the donor values, suggests a functional maintenance of memory T cells and naïve T lymphocytes in bronchial asthma. The increased proliferation of some T-cell subpopulations in asthmatics in remission suggests an activated state of memory T cells. The observed decrease in the number of CD4+TemCD62L+ and CD8+TemCD62L+ in patients with asthma exacerbation may be, by our opinion, associated with an active inflammatory process in the airways.

Sign in / Sign up

Export Citation Format

Share Document