Cross-protection and cross-reactive cytotoxic T cells induced by influenza virus vaccines in mice

1980 ◽  
Vol 10 (5) ◽  
pp. 396-401 ◽  
Author(s):  
Robert G. Webster ◽  
Brigitte A. Askonas
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Cytotoxic T Cells ◽  
Cross Protection

scholarly journals Role of viral infectivity in the induction of influenza virus-specific cytotoxic T cells.

1978 ◽  
Vol 147 (4) ◽  
pp. 1236-1252 ◽  
Author(s):  
T J Braciale ◽  
K L Yap
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Cell Response ◽  
Infectious Virus ◽  
Cytotoxic T Cells ◽  
T Cell Response ◽  
Cytotoxic T Cell

This report examines the requirement for infectious virus in the induction of influenza virus-specific cytotoxic T cells. Infectious influenza virus was found to be highly efficient at generating both primary and secondary cytotoxic T-cell response in vivo. Inactivated influenza virus however, failed to stimulate a detectable cytotoxic T-cell response in vivo even at immunizing doses 10(5)-10(6)-fold higher than the minimum stimulatory dose of infectious virus. Likewise inactivated virus failed to sensitize target cells for T cell-mediated lysis in vitro but could stimulate a specific cytotoxic response from primed cells in vitro. Possible requirements for the induction of virus-specific cytotoxic T-cell responses are discussed in light of these observations and those of other investigators.

Antibodies and CD4+ T-cells mediate cross-protection against H5N1 influenza virus infection in mice after vaccination with a low pathogenic H5N2 strain

Vaccine ◽  
2008 ◽  
Vol 26 (52) ◽  
pp. 6965-6974 ◽  
Author(s):  
Karoline Droebner ◽  
Emanuel Haasbach ◽  
Cordula Fuchs ◽  
Andreas O. Weinzierl ◽  
Stefan Stevanovic ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Virus Infection ◽  
Cd4 T Cells ◽  
Influenza Virus Infection ◽  
Cross Protection ◽  
H5n1 Influenza Virus ◽  
H5n1 Influenza

scholarly journals Suppression of Cytotoxic T Cell Functions and Decreased Levels of Tissue Resident Memory T cell During H5N1 infection

2020 ◽  
Author(s):  
Matheswaran Kandasamy ◽  
Kevin Furlong ◽  
Jasmine T. Perez ◽  
Santhakumar Manicassamy ◽  
Balaji Manicassamy
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Cytotoxic T Cells ◽  
Influenza Viruses ◽  
Viral Clearance ◽  
Virus Infections ◽  
Cell Functions

AbstractSeasonal influenza virus infections cause mild illness in healthy adults, as timely viral clearance is mediated by the functions of cytotoxic T cells. However, avian H5N1 influenza virus infections can result in prolonged and fatal illness across all age groups, which has been attributed to the overt and uncontrolled activation of host immune responses. Here we investigate how excessive innate immune responses to H5N1 impair subsequent adaptive T cell responses in the lungs. Using recombinant H1N1 and H5N1 strains sharing 6 internal genes, we demonstrate that H5N1 (2:6) infection in mice causes higher stimulation and increased migration of lung dendritic cells to the draining lymph nodes, resulting in higher numbers of virus specific T cells in the lungs. Despite robust T cell responses in the lungs, H5N1 (2:6) infected mice showed inefficient and delayed viral clearance as compared to H1N1 infected mice. In addition, we observed higher levels of inhibitory signals including increased PD1 and IL-10 expression by cytotoxic T cells in H5N1 (2:6) infected mice, suggesting that delayed viral clearance of H5N1 (2:6) was due to suppression of T cell functions in vivo. Importantly, H5N1 (2:6) infected mice displayed decreased numbers of tissue resident memory T cells as compared to H1N1 infected mice; however, despite decreased number of tissue resident memory T cells, H5N1 (2:6) were protected against a heterologous challenge from H3N2 virus (X31). Taken together, our study provides mechanistic insight for the prolonged viral replication and protracted illness observed in H5N1 infected patients.ImportanceInfluenza viruses cause upper respiratory tract infections in humans. In healthy adults, seasonal influenza virus infections result in mild disease. Occasionally, influenza viruses endemic in domestic birds can cause severe and fatal disease even in healthy individuals. In avian influenza virus infected patients, the host immune system is activated in an uncontrolled manner and is unable to control infection in a timely fashion. In this study, we investigated why the immune system fails to effectively control a modified form of avian influenza virus. Our studies show that T cell functions important for clearing virally infected cells are impaired by higher negative regulatory signals during modified avian influenza virus infection. In addition, memory T cell numbers were decreased in modified avian influenza virus infected mice. Our studies provide a possible mechanism for the severe and prolonged disease associated with avian influenza virus infections in humans.

scholarly journals Biological properties of an influenza A virus-specific killer T cell clone. Inhibition of virus replication in vivo and induction of delayed-type hypersensitivity reactions.

1981 ◽  
Vol 154 (2) ◽  
pp. 225-234 ◽  
Author(s):  
Y L Lin ◽  
B A Askonas
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Influenza A ◽  
Cytotoxic T Cells ◽  
Influenza Infection ◽  
Type A ◽  
Biological Properties ◽  
Influenza Viruses ◽  
Delayed Type Hypersensitivity ◽  
Hypersensitivity Skin

We tested two biological properties of a continuously growing mouse cytotoxic T cell line, L4, which is specific for influenza A virus and has been cloned and recloned many times. We previously reported that L4 cells are H-2 restricted and cross-reactive for all type A influenza viruses, whereas they do not recognize type B influenza viruses. They bear Thy-1 and Lyt-2 markers. In the present study, we show that L4 cytotoxic T cells protect mice against a lethal influenza infection on transfer to syngeneic recipients, and reduce virus titers in the lungs of mice challenged with a heterologous type A influenza virus. This provides further support for the active role of cytotoxic T cells in limiting virus replication in influenza infection. We could also demonstrate that the cloned cytotoxic T cells induce a delayed-type hypersensitivity skin reaction in the footpads of mice challenged with live or inactivated influenza virus. This reaction can be observed at 24 h, but has declined by 48 h. A clone of cells derived from L4 that has lost its cytotoxic potential and its ability to recognize infected cells did not induce a delayed-type hypersensitivity reaction in the presence of virus. Thus, cytotoxic T cells actively killing influenza virus-infected cells are able to induce a delayed-type hypersensitivity skin reaction to homologous and heterologous type A influenza viruses.

Cytotoxic T cells kill influenza virus infected cells but do not distinguish between serologically distinct type A viruses

Nature ◽  
1977 ◽  
Vol 267 (5609) ◽  
pp. 354-356 ◽  
Author(s):  
H. J. ZWEERINK ◽  
S. A. COURTNEIDGE ◽  
J. J. SKEHEL ◽  
M. J. CRUMPTON ◽  
BRIGITTE A. ASKONAS
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Cytotoxic T Cells ◽  
Distinct Type ◽  
Type A ◽  
Infected Cells

scholarly journals Quantitation of influenza virus antigens on infected target cells and their recognition by cross-reactive cytotoxic T cells.

1980 ◽  
Vol 151 (5) ◽  
pp. 1014-1025 ◽  
Author(s):  
C J Hackett ◽  
B A Askonas ◽  
R G Webster ◽  
K van Wyke
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
Influenza Virus ◽  
T Cell ◽  
Cytotoxic T Cells ◽  
Type A ◽  
Protein Molecule ◽  
M Protein ◽  
Target Cells ◽  
Infected Cells

Monoclonal antibody to type-A influenza virus matrix (M)-protein was used to quantitate the appearance of M-protein on abortively infected P815 cells. After 16 h of infection with different type-A viruses, only a low amount of M-protein appears on the surface of infected cells (approximately 10(3) site/cell) in contrast to approximately 10(5) hemagglutinin molecules on each cell surface. However, virus replication is required for M-protein appearance. Analysis of solubilized membranes purified from 16-h-infected cells shows approximately 10(4) M-protein molecule/cell in the plasma membrane, a content that is consistent with the observed low surface expression, and that indicates that most of the M-protein is localized internally. We found no evidence that cross-reactive cytotoxic T cells could recognize M-protein; neither monoclonal antibody or hyperimmune anti-M-protein antiserum could inhibit T cell killing, either alone or in combination with monoclonal anti-H-2 antibody. Taken together, the low level of M-protein appearance and lack of T cell blocking by anti-M-protein antibody leaves doubt that M-protein is the antigen recognized by cross-reactive cytotoxic T cells.

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