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 Vaccination with the RSV fusion protein formulated with a combination adjuvant induces long-lasting protective immunity

2014 ◽  
Vol 95 (5) ◽  
pp. 1043-1054 ◽  
Author(s):  
R. Garg ◽  
L. Latimer ◽  
V. Gerdts ◽  
A. Potter ◽  
S. van Drunen Littel-van den Hurk
Keyword(s):  
T Cells ◽  
Neutralizing Antibodies ◽  
Memory T Cells ◽  
Protective Efficacy ◽  
Affinity Maturation ◽  
Effector Memory ◽  
Polycytidylic Acid ◽  
Syncytial Virus ◽  
One Year ◽  
Tract Infections

Respiratory syncytial virus (RSV) is one of the primary causative agents of upper and lower respiratory tract infections in young children, in particular infants. Recently, we reported the protective efficacy of a RSV vaccine formulation consisting of a truncated version of the fusion (F) protein formulated with a Toll-like receptor (TLR) agonist and an immunostimulatory peptide in a carrier system (ΔF/TriAdj). To evaluate the duration of immunity induced by this vaccine candidate, we carried out long-term trials. The ΔF was formulated with triple adjuvant (TriAdj) containing either polyinosinic : polycytidylic acid (polyI : C) or cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs) and administered intranasally to mice. One year after the second vaccination all mice were challenged with RSV. Both ΔF/TriAdj formulations mediated the induction of high levels of IgG1, IgG2a and virus-neutralizing antibodies, and IgA in the lungs. Based on the numbers of IFN-γ- and IL-5-secreting cells in the spleen, the immune response was slightly T-helper cell type 1 (Th1)-biased. This was confirmed by the presence of F85–93-specific CD8+ effector T cells in the lungs of both ΔF/TriAdj(polyI : C)- and ΔF/TriAdj(CpG)-immunized mice. Both ΔF/TriAdj formulations induced RSV-specific CD8+ T cells. However, ΔF/TriAdj(polyI : C) generated significantly higher IgG affinity maturation and higher numbers of RSV-specific CD8+ effector memory T cells in lungs and CD8+ central memory T cells in spleen and lymph nodes than ΔF/TriAdj(CpG). After RSV challenge, no virus replication and no evidence of vaccine-induced pathology were detected in mice immunized with either of the ΔF/TriAdj formulations, demonstrating that the duration of immunity induced with these vaccines is at least one year.

scholarly journals Antigen-dependent proliferation and cytokine induction in respiratory syncytial virus-infected cotton rats reflect the presence of effector-memory T cells

Virology ◽  
2005 ◽  
Vol 337 (1) ◽  
pp. 102-110 ◽  
Author(s):  
Bettina W.M. Richter ◽  
Jaya M. Onuska ◽  
Stefan Niewiesk ◽  
Gregory A. Prince ◽  
Maryna C. Eichelberger
Keyword(s):  
T Cells ◽  
Respiratory Syncytial Virus ◽  
Memory T Cells ◽  
Effector Memory ◽  
Cytokine Induction ◽  
Effector Memory T Cells ◽  
Cotton Rats ◽  
Syncytial Virus

scholarly journals Differential Mucin Expression by Respiratory Syncytial Virus and Human Metapneumovirus Infection in Human Epithelial Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Ma. Del Rocío Baños-Lara ◽  
Boyang Piao ◽  
Antonieta Guerrero-Plata
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Epithelial Cells ◽  
Viral Infections ◽  
Human Metapneumovirus ◽  
Human Epithelial Cells ◽  
Mucin Expression ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Disease

Mucins (MUC) constitute an important component of the inflammatory and innate immune response. However, the expression of these molecules by respiratory viral infections is still largely unknown. Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two close-related paramyxoviruses that can cause severe low respiratory tract disease in infants and young children worldwide. Currently, there is not vaccine available for neither virus. In this work, we explored the differential expression of MUC by RSV and hMPV in human epithelial cells. Our data indicate that the MUC expression by RSV and hMPV differs significantly, as we observed a stronger induction of MUC8, MUC15, MUC20, MUC21, and MUC22 by RSV infection while the expression of MUC1, MUC2, and MUC5B was dominated by the infection with hMPV. These results may contribute to the different immune response induced by these two respiratory viruses.

scholarly journals Potential Neurocognitive Symptoms Due to Respiratory Syncytial Virus Infection

Pathogens ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 47
Author(s):  
Catalina A. Andrade ◽  
Alexis M. Kalergis ◽  
Karen Bohmwald
Keyword(s):  
Respiratory Syncytial Virus ◽  
Viral Infections ◽  
Respiratory Infections ◽  
The Elderly ◽  
Cell Types ◽  
Potential Effect ◽  
Viral Agent ◽  
Pulmonary Manifestations ◽  
Syncytial Virus ◽  
Tract Infections

Respiratory infections are among the major public health burdens, especially during winter. Along these lines, the human respiratory syncytial virus (hRSV) is the principal viral agent causing acute lower respiratory tract infections leading to hospitalization. The pulmonary manifestations due to hRSV infection are bronchiolitis and pneumonia, where the population most affected are infants and the elderly. However, recent evidence suggests that hRSV infection can impact the mother and fetus during pregnancy. Studies have indicated that hRSV can infect different cell types from the placenta and even cross the placenta barrier and infect the fetus. In addition, it is known that infections during the gestational period can lead to severe consequences for the development of the fetus due not only to a direct viral infection but also because of maternal immune activation (MIA). Furthermore, it has been described that the development of the central nervous system (CNS) of the fetus can be affected by the inflammatory environment of the uterus caused by viral infections. Increasing evidence supports the notion that hRSV could invade the CNS and infect nervous cells, such as microglia, neurons, and astrocytes, promoting neuroinflammation. Moreover, it has been described that the hRSV infection can provoke neurological manifestations, including cognitive impairment and behavioral alterations. Here, we will review the potential effect of hRSV in brain development and the potential long-term neurological sequelae.

scholarly journals In vitro maintaining of CD4+ central and effector memory cells in normal and inflammatory conditions

2020 ◽  
Vol 22 (5) ◽  
pp. 837-846
Author(s):  
E. A. Blinova ◽  
A. V. Kolerova ◽  
V. E. Balyasnikov ◽  
V. A. Kozlov
Keyword(s):  
T Cells ◽  
Memory T Cells ◽  
Cell Receptor ◽  
Whole Body ◽  
Effector Memory ◽  
Adherent Cell ◽  
Memory Cells ◽  
Inflammatory Conditions ◽  
Low Sensitivity

IL-7 is a key factor for the survival and maintenance of CD4+ central (Tcm) and effector (Tem) memory cells in the whole body. In many autoimmune diseases, an elevated level of IL-7 is detected in blood serum and at the site of inflammation, thus suggesting participation of this homeostatic factor in the survival of memory T cells, including auto-reactive clones, in inflammatory disorders. The aim of the study was to investigate the mechanisms of maintaining CD4+ memory T cells under normal and inflammatory conditions. We developed an in vitro model of inflammation, based on induction of pro-inflammatory cytokines, and then evaluated the effects of IL-7 upon purified sorted populations of CD4+Tcm and Tem under normal conditions and in vitro inflammatory model. IL-7 treatment promoted maintenance of CD4+Tcm phenotype in all variants of cultures. In the absence of contact with adherent cell fraction, the IL-7-induced proliferation of Tcm and Tem was slightly reduced, both under normal and inflammatory conditions, thus suggesting low sensitivity of memory T cells to contacts with MHC, and, probably, a requirement for additional signals to provide complete stimulation with IL-7. The last suggestion is also supported by data about CD127 and CD132 expression, i.e., in the absence of contact with MHC, the proportion of CD127+CD132+ cells was decreased in both subpopulations of CD4+ memory cells. Upon in vitro cultures, IL-7 contributed to decreased expression of CD127, and increased expression of CD132 on CD4+Tcm and Tem. We have evaluated the CD4+Tcm and Tem populations by affinity of T cell receptor (TCR), using the level of CD5 expression. Т cells with high TCR affinity for self-antigens are known to have higher expression of CD5. In comparison to Tem, the Tcm contained more CD5high cells. In cultures, IL-7 promoted a high level of CD5 expression on Tcm, which was comparable to levels observed in peripheral blood cells. High CD5 expression on Tem was observed after stimulation with IL-7 in the in vitro inflammatory model. In the absence of contact with MHC, the number of CD5high cells decreased among CD4+Tem and Tcm. Thus, CD4+Tcm cells with high affinity for autologous antigens are probably dependent on the presence of homeostatic factors, in particular, IL-7, and contacts with antigen-presenting cells (APCs). Under conditions of inflammation, no changes were revealed in the mechanism of maintaining CD4+Tcm, in contrast to CD4+Tem. Being less dependent on IL-7 under normal conditions, CD4+CD5highTem are accumulated in the presence of IL-7 under in vitro inflammatory conditions.

Host-Reactive Donor CD8+ T Memory Stem Cells but Not Mature T Memory Cells Primed Against Leukemic Cells Mediate Potent Graft-Versus-Leukemia Effect.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 190-190
Author(s):  
Elizabeth O. Hexner ◽  
Dale Frank ◽  
Stephen G. Emerson ◽  
Yi Zhang
Keyword(s):  
Stem Cells ◽  
T Cells ◽  
T Cell ◽  
Adoptive Transfer ◽  
Memory T Cells ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Effector Memory ◽  
Memory Cells ◽  
Alloreactive T Cell

Abstract The potent ability of allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and donor leukocyte infusion (DLI) to cure leukemia remains the most striking example of the ability of the immune system to recognize and destroy tumors. Unfortunately, both allo-HSCT and DLI are often complicated by graft-versus-host disease (GVHD). In addition, durable responses to conventional DLI for acute leukemias have been disappointing. A better understanding of the mechanisms of alloreactive T cell-mediated anti-leukemia activity will be important for separating the GVL effect from GVHD. Adoptive transfer of selected subsets of T cells specific for miHA- or leukemia associated antigens might offer the chance to maximize GVL while minimizing GVHD. Using mouse models of human GVHD directed against miHAs, we recently demonstrated that antigen-experienced CD44loCD62LhiCD8+ T cells contain T memory stem cells that have greater ability than naïve T cells and mature memory T cells to proliferate and generate alloreactive effector cells and all memory T cell subsets (Nature Medicine, 2005, 11:1299). Using the same mouse model, we have now found that although B6/SJL mice receiving donor CD44hiCD8+ T cells (mature memory cells) primed against B6 mouse-derived myeloid leukemia C1498 cells do not develop clinical GVHD, most will die from C1498 leukemia by day 45 following injection of C1498 cells. Adoptive transfer of CD44loCD8+ T cells primed against C1498 leukemic cells caused clinical GVHD, but the majority of recipients (75%) survived long term free of C1498 leukemia. Surprisingly, the GVL effect of donor CD44loCD8+ T cells primed against C1498 leukemia cells was significantly inhibited when C1498 leukemia cell-primed CD44hiCD8+ T cells and CD44loCD8+ T cells were co-injected into B6/SJL mice, with only 25% of the mice surviving without leukemia. These results suggest that while the GVL effect is clearly mediated by antigen experienced CD44loCD8+ T cells, CD44hiCD8+ T memory cells primed against tumor cells are not only functionally defective in eliminating leukemia cells but are also potent inhibitors of alloreactive T cell-mediated GVL activity. We found that host-reactive effector memory CD8+ T cells produced 10-fold higher IL-10 than unstimulated naïve T cells and T memory stem cells, while CD8+ T memory stem cells expressed upregulated IL-10 receptors. These findings suggest that the inhibitory effect of mature memory T cells on alloreactive T cell-mediated GVL effect may be associated with increased production of IL-10 by mature memory cells and/or enhanced susceptibility of T memory stem cells to IL-10 secreted by mature memory cells. In addition, host dendritic cell activation of donor CD8+ naïve T cells progressively induced the generation of memory stem cells (CD44loCD62LhiSca-1hi), central memory cells (CD44hiCD62Lhi) and effector memory cells (CD44hiCD62Llo). CD8+ T memory stem cells displayed a TCR V-beta repertoire similar to that of unstimulated naive T cells. In contrast, both central memory and effector memory T cells showed a skewed TCR V-beta repertoire. Thus, selective elimination of suppressive CD44hiCD8+ T cells may represent an approach to augmenting GVL activity while preserving a diverse TCR V-beta repertoire.

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 Immunological, Viral, Environmental, and Individual Factors Modulating Lung Immune Response to Respiratory Syncytial Virus

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Silvia Vandini ◽  
Paolo Bottau ◽  
Giacomo Faldella ◽  
Marcello Lanari
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Animal Models ◽  
Respiratory Tract Infections ◽  
Clinical Course ◽  
Respiratory Infections ◽  
Syncytial Virus ◽  
High Risk Infants ◽  
Tract Infections ◽  
Lung Response

Respiratory syncytial virus is a worldwide pathogen agent responsible for frequent respiratory tract infections that may become severe and potentially lethal in high risk infants and adults. Several studies have been performed to investigate the immune response that determines the clinical course of the infection. In the present paper, we review the literature on viral, environmental, and host factors influencing virus response; the mechanisms of the immune response; and the action of nonimmunological factors. These mechanisms have often been studied in animal models and in the present review we also summarize the main findings obtained from animal models as well as the limits of each of these models. Understanding the lung response involved in the pathogenesis of these respiratory infections could be useful in improving the preventive strategies against respiratory syncytial virus.

scholarly journals Tissue-Resident Memory T Cells in the Lungs Protect against Acute Respiratory Syncytial Virus Infection

2021 ◽  
Vol 5 (2) ◽  
pp. 59-69
Author(s):  
Mitchell A. Luangrath ◽  
Megan E. Schmidt ◽  
Stacey M. Hartwig ◽  
Steven M. Varga
Keyword(s):  
T Cells ◽  
Respiratory Syncytial Virus ◽  
Virus Infection ◽  
Respiratory Syncytial Virus Infection ◽  
Memory T Cells ◽  
Syncytial Virus ◽  
Resident Memory T Cells

scholarly journals Type III interferons disrupt the lung epithelial barrier upon viral recognition

2020 ◽  
Author(s):  
Achille Broggi ◽  
Sreya Ghosh ◽  
Benedetta Sposito ◽  
Roberto Spreafico ◽  
Fabio Balzarini ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Infections ◽  
Rna Virus ◽  
Virus Infections ◽  
Highly Pathogenic ◽  
Type Iii ◽  
Lung Epithelial ◽  
Syncytial Virus ◽  
Tract Infections ◽  
Viral Recognition

AbstractLower respiratory tract infections are a leading cause of mortality driven by infectious agents. RNA viruses such as influenza virus, respiratory syncytial virus and the new pandemic coronavirus SARS-CoV-2 can be highly pathogenic. Clinical and experimental evidence indicate that most severe and lethal cases do not depend on the viral burden and are, instead, characterized by an aberrant immune response. In this work we assessed how the innate immune response contributes to the pathogenesis of RNA virus infections. We demonstrate that type III interferons produced by dendritic cells in the lung in response to viral recognition cause barrier damage and compromise the host tissue tolerance. In particular, type III interferons inhibit tissue repair and lung epithelial cell proliferation, causing susceptibility to lethal bacterial superinfections. Overall, our data give a strong mandate to rethink the pathophysiological roles of this group of interferons and their possible use in the clinical practice against endemic as well as emerging viral infections.

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