scholarly journals Activity of Negative Regulation of the PD-1/PD-L1/PD-L2 T-Cell Response System in Patients with Pneumonia and Influenza A (H1N1)

2021 ◽  
Vol 17 (4) ◽  
pp. 4-11
Author(s):  
A. V. Malyarchikov ◽  
K. G. Shаpovаlov ◽  
S. A. Lukyanov ◽  
P. P. Tereshkov ◽  
L. S. Kazantseva
Keyword(s):  
T Cell ◽  
Cell Response ◽  
Plasma Levels ◽  
Influenza A ◽  
Severe Pneumonia ◽  
T Cell Response ◽  
Negative Regulation ◽  
Regulation System ◽  
Flow Cytofluorometry ◽  
Influenza A H1n1

Systemic inflammation is an integral pathophysiological component of many critical illnesses. The systemic inflammatory response is based on a cascade of interactions leading to hypercytokinemia and, as a consequence, multiple organ failure, which is one of the main causes of mortality in intensive care units.Aim of the study. To evaluate the activity of the negative regulation system of T-cell response by determining the plasma levels of PD-1, PD-L1 and PD-L2 molecules in pneumonia patients with influenza A (H1N1).Materials and methods. 85 patients with pneumonia and underlying influenza A (H1N1) were examined. Among them there were 30 patients with severe pneumonia, and 55 patients with non-severe pneumonia. Plasma levels of PD-1, PD-L1, PD-L2 molecules was determined by flow cytofluorometry method.Results. In patients with severe pneumonia and underlying influenza A (H1N1), the plasma level of PD-1 receptor increased 4.6-fold, while the concentration of its ligands PD-L1 and PD-L2 increased 10.6 and 2.2-fold, respectively.Conclusion. Significant increase in levels of PD-1 and its ligands PD-L1 and PD-L2 in patients with pneumonia and underlying influenza A (H1N1) indicates the involvement of negative regulation system of T-cell response in the cascade of immunological reactions and is associated with the severe disease. Possible correction of immune reactions realized through PD-1/PD-L1/PD-L2 complex in critically ill patients is a promising research avenue.

scholarly journals PD-L1 expression induced by the 2009 pandemic influenza A(H1N1) virus impairs the human T cell response

2013 ◽  
Vol 4 ◽  
Author(s):  
Valero-Pacheco Nuriban ◽  
Mora-Velandia Luz Mar�a ◽  
Arriaga-Pizano Lourdes ◽  
Ferat-Osorio Eduardo ◽  
Pastelin-Palacios Rodolfo ◽  
...  
Keyword(s):  
T Cell ◽  
Pandemic Influenza ◽  
Cell Response ◽  
Influenza A ◽  
H1n1 Virus ◽  
T Cell Response ◽  
Human T Cell ◽  
Influenza A H1n1

scholarly journals Mucosal CD8+ T cell responses induced by an MCMV based vaccine vector confer protection against influenza challenge

2018 ◽  
Author(s):  
Xiaoyan Zheng ◽  
Jennifer Dora Oduro ◽  
Julia Désirée Boehme ◽  
Lisa Borkner ◽  
Thomas Ebensen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Response ◽  
Influenza A ◽  
Clinical Medicine ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Vaccine Vector ◽  
Protective Capacity

Cytomegalovirus (CMV) is a ubiquitous β-herpesvirus that establishes life-long latent infection in a high percentage of the population worldwide. CMV induces the strongest and most durable CD8+ T cell response known in human clinical medicine. Due to its unique properties, the virus represents a promising candidate vaccine vector for the induction of persistent cellular immunity. To take advantage of this, we constructed a recombinant murine CMV (MCMV) expressing an MHC-I restricted epitope from influenza A virus (IAV) H1N1 within the immediate early 2 (ie2) gene. Only mice that were immunized intranasally (i.n.) were capable of controlling IAV infection, despite the greater potency of the intraperitoneally (i.p.) vaccination in inducing a systemic IAV-specific CD8+ T cell response. The protective capacity of the i.n. immunization was associated with its ability to induce IAV-specific tissue-resident memory CD8+ T (CD8TRM) cells in the lungs. Our data demonstrate that the protective effect exerted by the i.n. immunization was critically mediated by antigen-specific CD8+ T cells. CD8TRM cells promoted the induction of IFNγ and chemokines that facilitate the recruitment of antigen-specific CD8+ T cells to the lungs. Overall, our results showed that locally applied MCMV vectors could induce mucosal immunity at sites of entry, providing superior immune protection against respiratory infections.

scholarly journals Influenza A Virus Infection Results in a Robust, Antigen-Responsive, and Widely Disseminated Foxp3+ Regulatory T Cell Response

2011 ◽  
Vol 86 (5) ◽  
pp. 2817-2825 ◽  
Author(s):  
R. J. Betts ◽  
N. Prabhu ◽  
A. W. S. Ho ◽  
F. C. Lew ◽  
P. E. Hutchinson ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Regulatory T Cell ◽  
Cell Response ◽  
Influenza A ◽  
T Cell Response ◽  
Influenza A Virus Infection

scholarly journals Rectification of Age-Associated Deficiency in Cytotoxic T Cell Response to Influenza A Virus by Immunization with Immune Complexes

2007 ◽  
Vol 179 (9) ◽  
pp. 6153-6159 ◽  
Author(s):  
Biao Zheng ◽  
Yongxin Zhang ◽  
Hongxia He ◽  
Ekaterina Marinova ◽  
Kirsten Switzer ◽  
...  
Keyword(s):  
T Cell ◽  
Influenza A Virus ◽  
Immune Complexes ◽  
Cell Response ◽  
Influenza A ◽  
T Cell Response ◽  
Cytotoxic T Cell

scholarly journals Human Influenza A Virus–Specific CD8+ T-Cell Response Is Long-lived

2015 ◽  
Vol 212 (1) ◽  
pp. 81-85 ◽  
Author(s):  
Carolien E. van de Sandt ◽  
Marine L. B. Hillaire ◽  
Martina M. Geelhoed-Mieras ◽  
Albert D. M. E. Osterhaus ◽  
Ron A. M. Fouchier ◽  
...  
Keyword(s):  
T Cell ◽  
Influenza A Virus ◽  
Cell Response ◽  
Influenza A ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Human Influenza

Rapid T Cell Response to Vaccination Can Occur without Antibody Response in Children Post HSCT.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2235-2235
Author(s):  
W. Nicholas Haining ◽  
J. Evans ◽  
N. Seth ◽  
G. Callaway ◽  
K. Wucherpfennig ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Cell Response ◽  
Influenza A ◽  
T Cell Response ◽  
T Cell Memory ◽  
Cell Immunity ◽  
Before And After ◽  
B Cell Response

Abstract Vaccination is widely used to improve pathogen-specific immunity in patients post HSCT, but it is not known whether patients can mount an effective T cell response to vaccine antigens (vAg). Moreover the relationship between T and B cell response to vAg has not been studied. We hypothesized that a sufficiently sensitive assay of T cell response to vAg would allow vaccination to be used as a tool to measure immune recovery post HSCT and improve vaccine design. We therefore: (1) developed a flow-cytometry-based approach to quantify and characterize T cells specific for vAg; (2) validated it by measuring T cell immunity to influenza A in normal donors; and (3) characterized the T and B cell response to influenza vaccination in pediatric HSCT patients. PBMC were labeled with CFSE and stimulated in vitro with whole influenza Ag. Ag-specific T cells were sensitively detected by their proliferation (loss of CFSE fluorescence) and simultaneous expression of the activation marker HLA-DR. Proliferating/active T cells could be readily detected after stimulation with influenza A Ag in healthy adult (n=4) and pediatric (n=19) donors but were absent in control conditions. Both CD4+ and CD8+ T cell proliferation was detected in all donors but one, and in children as young as 6mo. Staining with MHC I- and MHC II-tetramers confirmed that the proliferating/active population contained T cells specific for immunodominant CD8+ and CD4+ epitopes, demonstrating that vAg were processed and presented to epitope-specific T cells. To characterize the phenotype of influenza-specific T cell memory, we separated memory and naive CD4+ cells prior to antigen-stimulation. Antigen-experienced (CD45RA−/CCR7−) but not naive (CD45RA+/CCR7+) T cells proliferated to vAg confirming that the assay detected pre-existing influenza-A-specific T cell memory. We next assessed Influenza-A-specific T cell immunity before and after influenza vaccination in five pediatric HSCT recipients (mean age 10.6y, range 5–15y; mean time from transplant 13m, range 3–21m). Prior to vaccination the CD4 proliferation to influenza-A was a mean of 3.3% (range 0.04–11%). Following vaccination CD4 proliferation increased significantly in all patients (mean 19.0%, range 6.9%–31.8%, p=0.02). This increase was specific as proliferation to control Ag was unchanged. Influenza-A CD8+ proliferation also increased in 3 of 5 patients but was not statistically significant for the group consistent with the limited efficacy of soluble vAg in inducing CD8+ T cell response. All patients had detectable influenza-A-specific IgG levels prior to vaccination but despite a T cell response to vaccination in all patients, none had a significant increase in IgG level following vaccination. Only one patient had an IgM response; this patient also had the highest influenza-A-specific CD4 proliferation before and after immunization suggesting that there may be a threshold of T cell response required for a B cell response. Using a novel assay we demonstrate that a T cell response to vaccination can occur without an accompanying B cell response. This assay provides a more sensitive measure of immunity to vaccination and allows vaccine response to be used as a benchmark of strategies to accelerate post-HSCT T cell reconstitution.

scholarly journals Hemagglutinin-specific cytotoxic T-cell response during influenza infection.

1977 ◽  
Vol 146 (3) ◽  
pp. 893-898 ◽  
Author(s):  
F A Ennis ◽  
W J Martin ◽  
M W Verbonitz
Keyword(s):  
T Cell ◽  
Target Cell ◽  
Cell Response ◽  
Influenza A ◽  
Influenza Infection ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Target Cells ◽  
Cervical Lymph Nodes ◽  
Cytotoxic Response

Specific cytotoxic thymus-derived (T) lymphocytes were detected in the cervical lymph nodes and spleen during influenza infection of mice. The cytotoxic T cells can distinguish target cells infected with different influenza A subtypes. Infection with parent viruses and their recombinant progeny possessing the hemagglutinin of one parent and the neuraminidase of the other demonstrated that significant cytotoxicity occurred only when the hemagglutinin of the immunizing viruses was the same as that of the virus used to infect the target cell. In addition to this specific cytotoxic response to the major surface antigen, a cross-reactive response could be detected when the relatively nonpermissive L cell was used as the target cell. These results indicate there is a specific cytotoxic T-cell response to the surface hemagglutinin, and a cross-reactive cytotoxic response, not directed to the hemagglutinin, during influenza infection. The cytotoxic T-cell response specific for the hemagglutinin antigen may play an important role in in vivo immunity to influenza.

scholarly journals Plasmacytoid Dendritic Cells Require Direct Infection To Sustain the Pulmonary Influenza A Virus-Specific CD8 T Cell Response

2015 ◽  
Vol 90 (6) ◽  
pp. 2830-2837 ◽  
Author(s):  
Emily A. Hemann ◽  
Louisa E. Sjaastad ◽  
Ryan A. Langlois ◽  
Kevin L. Legge
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Response ◽  
Influenza A ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Cross Presentation ◽  
Cell Responses ◽  
Presentation Pathway

ABSTRACTFollowing influenza A virus (IAV) infection, development of a robust IAV-specific CD8 T cell response is required for clearance of primary infection and enhances memory protection. Following IAV infection, plasmacytoid dendritic cells (pDC) or CD8α+DC regulate pulmonary effector CD8 T cell responses within the lung. Without this DC-T cell interaction, insufficient effector CD8 T cells are maintained in the lungs, leading to enhanced morbidity and mortality. Previous studies have demonstrated that pDC are capable of classical presentation or cross-presentation of IAV antigens and could potentially regulate IAV-specific CD8 T cell responses through either mechanism. Our results demonstrate that pDC from the lungs of donor mice infected with an IAV that is not able to replicate in hematopoietic cells (142t-IAV), unlike donor pDC isolated from the lungs of control infected mice, are not able to rescue the host IAV-specific CD8 T cell response from apoptosis. This indicates that pDC must utilize the direct presentation pathway for this rescue. This inability of pDC from 142t-IAV donors to rescue the IAV-specific CD8 T cell response is not due to differences in the overall ability of 142t-IAV to replicate within the lungs or generate defective viral genomes or to differences in levels of costimulatory molecules required for this interaction. We further demonstrate that bypassing the antigen presentation pathway by coating the 142t-IAV pDC with IAV peptide epitopes restores their ability to rescue the IAV-specific CD8 T cell response.IMPORTANCEIAV continues to be a global health burden, infecting 5 to 20% of the global population annually. Continued investigation into the mechanisms that mediate protective immune responses against IAV is important to improving current vaccination and antiviral strategies antagonistic toward IAV. Our findings presented herein demonstrate a key requirement for pDC promotion of effector CD8 T cell survival: that rather than utilizing cross-presentation, pDC must be infected and utilize the endogenous pathway for presentation of antigens to CD8 T cells duringin vivoIAV infections. This suggests that targeting presentation via the endogenous pathway in pDC could be important for the development of unique antiviral cellular therapies.

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