Cytotoxic T Cells in the Lungs of Mice Infected with an Influenza A Virus

Human influenza A virus-specific, cytotoxic T cells have been shown previously to recognize the virus nucleoprotein on infected cells. CTL preparations from four HLA B37-positive donors were shown to recognize a synthetic peptide that corresponded to amino acids 335-349 of the nucleoprotein sequence. Influenza-specific CTL from 10 donors of other HLA types failed to recognize this epitope. CD8+ CTL lines were derived from lymphocytes of two HLA B37-positive donors and used to show that the peptide was represented on virus-infected cells and to determine the probable boundaries of the epitope.

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Cross-Reactivity between Hepatitis C Virus and Influenza A Virus Determinant-Specific Cytotoxic T Cells

Journal of Virology ◽

10.1128/jvi.75.23.11392-11400.2001 ◽

2001 ◽

Vol 75 (23) ◽

pp. 11392-11400 ◽

Cited By ~ 170

Author(s):

Heiner Wedemeyer ◽

Eishiro Mizukoshi ◽

Anthony R. Davis ◽

Jack R. Bennink ◽

Barbara Rehermann

Keyword(s):

T Cells ◽

Hepatitis C Virus ◽

Hepatitis C ◽

T Cell ◽

Influenza A Virus ◽

Influenza A ◽

Blood Donors ◽

Cytotoxic T Cells ◽

Target Cells ◽

Memory Cells

ABSTRACT The cellular immune response contributes to viral clearance as well as to liver injury in acute and chronic hepatitis C virus (HCV) infection. An immunodominant determinant frequently recognized by liver-infiltrating and circulating CD8+ T cells of HCV-infected patients is the HCVNS3-1073 peptide CVNGVCWTV. Using a sensitive in vitro technique with HCV peptides and multiple cytokines, we were able to expand cytotoxic T cells specific for this determinant not only from the blood of 11 of 20 HCV-infected patients (55%) but also from the blood of 9 of 15 HCV-negative blood donors (60%), while a second HCV NS3 determinant was recognized only by HCV-infected patients and not by seronegative controls. The T-cell response of these healthy blood donors was mediated by memory T cells, which cross-reacted with a novel T-cell determinant of the A/PR/8/34 influenza A virus (IV) that is endogenously processed from the neuraminidase (NA) protein. Both the HCV NS3 and the IV NA peptide displayed a high degree of sequence homology, bound to the HLA-A2 molecule with high affinity, and were recognized by cytotoxic T lymphocytes with similar affinity (10−8 M). Using the HLA-A2-transgenic mouse model, we then demonstrated directly that HCV-specific T cells could be induced in vivo by IV infection. Splenocytes harvested from IV-infected mice at the peak of the primary response (day 7 effector cells) or following complete recovery (day 21 memory cells) recognized the HCV NS3 peptide, lysed peptide-pulsed target cells, and produced gamma interferon. These results exemplify that host responses to an infectious agent are influenced by cross-reactive memory cells induced by past exposure to heterologous viruses, which could have important consequences for vaccine development.

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Faculty Opinions recommendation of Pulmonary immunization with a recombinant influenza A virus vaccine induces lung-resident CD4+ memory T cells that are associated with protection against tuberculosis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733830332.793575822 ◽

2020 ◽

Author(s):

Gabrielle Belz

Keyword(s):

T Cells ◽

Influenza A Virus ◽

Virus Vaccine ◽

Influenza A ◽

Memory T Cells

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Tbx21 and Foxp3 Are Epigenetically Stabilized in T-Bet+ Tregs That Transiently Accumulate in Influenza A Virus-Infected Lungs

International Journal of Molecular Sciences ◽

10.3390/ijms22147522 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7522

Author(s):

Yassin Elfaki ◽

Juhao Yang ◽

Julia Boehme ◽

Kristin Schultz ◽

Dunja Bruder ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Influenza A Virus ◽

Influenza A ◽

T Cell Subsets ◽

T Helper 1 ◽

T Box ◽

Cell Responses ◽

Accumulation Kinetics ◽

Kinetics Of

During influenza A virus (IAV) infections, CD4+ T cell responses within infected lungs mainly involve T helper 1 (Th1) and regulatory T cells (Tregs). Th1-mediated responses favor the co-expression of T-box transcription factor 21 (T-bet) in Foxp3+ Tregs, enabling the efficient Treg control of Th1 responses in infected tissues. So far, the exact accumulation kinetics of T cell subsets in the lungs and lung-draining lymph nodes (dLN) of IAV-infected mice is incompletely understood, and the epigenetic signature of Tregs accumulating in infected lungs has not been investigated. Here, we report that the total T cell and the two-step Treg accumulation in IAV-infected lungs is transient, whereas the change in the ratio of CD4+ to CD8+ T cells is more durable. Within lungs, the frequency of Tregs co-expressing T-bet is steadily, yet transiently, increasing with a peak at Day 7 post-infection. Interestingly, T-bet+ Tregs accumulating in IAV-infected lungs displayed a strongly demethylated Tbx21 locus, similarly as in T-bet+ conventional T cells, and a fully demethylated Treg-specific demethylated region (TSDR) within the Foxp3 locus. In summary, our data suggest that T-bet+ but not T-bet− Tregs are epigenetically stabilized during IAV-induced infection in the lung.

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Protection against Streptococcus pneumoniae Invasive Pathogenesis by a Protein-Based Vaccine Is Achieved by Suppression of Nasopharyngeal Bacterial Density during Influenza A Virus Coinfection

Infection and Immunity ◽

10.1128/iai.00530-16 ◽

2016 ◽

Vol 85 (2) ◽

Cited By ~ 12

Author(s):

M. Nadeem Khan ◽

Qingfu Xu ◽

Michael E. Pichichero

Keyword(s):

T Cells ◽

Streptococcus Pneumoniae ◽

Influenza A Virus ◽

Influenza A ◽

Passive Transfer ◽

Bacterial Density ◽

Content Type ◽

Adult Mice ◽

Significant Difference ◽

Colonization Density

ABSTRACTAn increase inStreptococcus pneumoniaenasopharynx (NP) colonization density during a viral coinfection initiates pathogenesis. To mimic naturalS. pneumoniaepathogenesis, we commensally colonized the NPs of adult C57BL/6 mice withS. pneumoniaeserotype (ST) 6A or 8 and then coinfected them with mouse-adapted H1N1 influenza A virus (PR/8/34).S. pneumoniaeestablished effective commensal colonization, and influenza virus coinfection causedS. pneumoniaeNP density to increase, resulting in bacteremia and mortality. We then studied histidine triad protein D (PhtD), anS. pneumoniaeadhesin vaccine candidate, for its ability to prevent invasiveS. pneumoniaedisease in adult and infant mice. In adult mice, the efficacy of PhtD vaccination was compared with that of PCV13. Vaccination with PCV13 led to a greater reduction ofS. pneumoniaeNP density (>2.5 log units) than PhtD vaccination (∼1-log-unit reduction). However, no significant difference was observed with regard to the prevention ofS. pneumoniaebacteremia, and there was no difference in mortality. Depletion of CD4+T cells in PhtD-vaccinated adult mice, but not PCV13-vaccinated mice, caused a loss of vaccine-induced protection. In infant mice, passive transfer of antisera or CD4+T cells from PhtD-vaccinated adult mice led to a nonsignificant reduction in NP colonization density, whereas passive transfer of antisera and CD4+T cells was needed to cause a significant reduction in NP colonization density. For the first time, these data show an outcome with regard to prevention of invasiveS. pneumoniaepathogenesis with a protein vaccine similar to that which occurs with a glycoconjugate vaccine despite a less robust reduction in NP bacterial density.

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Recognition of the Viral Nucleoprotein by Influenza a Specific Cytotoxic T Cells

Immune Regulation ◽

10.1007/978-1-4612-4996-2_29 ◽

1985 ◽

pp. 231-241 ◽

Cited By ~ 1

Author(s):

A. R. M. Townsend ◽

A. J. McMichael ◽

G. G. Brownlee

Keyword(s):

T Cells ◽

Influenza A ◽

Cytotoxic T Cells

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Exacerbation of Influenza A Virus Disease Severity by Respiratory Syncytial Virus Co-Infection in a Mouse Model

Viruses ◽

10.3390/v13081630 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1630 ◽

Cited By ~ 1

Author(s):

Junu A. George ◽

Shaikha H. AlShamsi ◽

Maryam H. Alhammadi ◽

Ahmed R. Alsuwaidi

Keyword(s):

T Cells ◽

Respiratory Syncytial Virus ◽

Influenza A Virus ◽

Influenza A ◽

Immune Cell ◽

Virus Disease ◽

Viral Loads ◽

Syncytial Virus

Influenza A virus (IAV) and respiratory syncytial virus (RSV) are leading causes of childhood infections. RSV and influenza are competitive in vitro. In this study, the in vivo effects of RSV and IAV co-infection were investigated. Mice were intranasally inoculated with RSV, with IAV, or with both viruses (RSV+IAV and IAV+RSV) administered sequentially, 24 h apart. On days 3 and 7 post-infection, lung tissues were processed for viral loads and immune cell populations. Lung functions were also evaluated. Mortality was observed only in the IAV+RSV group (50% of mice did not survive beyond 7 days). On day 3, the viral loads in single-infected and co-infected mice were not significantly different. However, on day 7, the IAV titer was much higher in the IAV+RSV group, and the RSV viral load was reduced. CD4 T cells were reduced in all groups on day 7 except in single-infected mice. CD8 T cells were higher in all experimental groups except the RSV-alone group. Increased airway resistance and reduced thoracic compliance were demonstrated in both co-infected groups. This model indicates that, among all the infection types we studied, infection with IAV followed by RSV is associated with the highest IAV viral loads and the most morbidity and mortality.

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