scholarly journals Stochastic Expansions Maintain the Clonal Stability of CD8+ T Cell Populations Undergoing Memory Inflation Driven by Murine Cytomegalovirus

2019 ◽  
Vol 204 (1) ◽  
pp. 112-121 ◽  
Author(s):  
Corinne J. Smith ◽  
Vanessa Venturi ◽  
Maire F. Quigley ◽  
Holly Turula ◽  
Emma Gostick ◽  
...  
2018 ◽  
Vol 9 ◽  
Author(s):  
Kaitlyn M. Morabito ◽  
Tracy J. Ruckwardt ◽  
Erez Bar-Haim ◽  
Deepika Nair ◽  
Syed M. Moin ◽  
...  

2009 ◽  
Vol 183 (6) ◽  
pp. 3932-3941 ◽  
Author(s):  
Christopher M. Snyder ◽  
Andrea Loewendorf ◽  
Elizabeth L. Bonnett ◽  
Michael Croft ◽  
Chris A. Benedict ◽  
...  

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 956
Author(s):  
Kirsten Freitag ◽  
Sara Hamdan ◽  
Matthias J. Reddehase ◽  
Rafaela Holtappels

CD8+ T-cell responses to pathogens are directed against infected cells that present pathogen-encoded peptides on MHC class-I molecules. Although natural responses are polyclonal, the spectrum of peptides that qualify for epitopes is remarkably small even for pathogens with high coding capacity. Among those few that are successful at all, a hierarchy exists in the magnitude of the response that they elicit in terms of numbers of CD8+ T cells generated. This led to a classification into immunodominant and non-immunodominant or subordinate epitopes, IDEs and non-IDEs, respectively. IDEs are favored in the design of vaccines and are chosen for CD8+ T-cell immunotherapy. Using murine cytomegalovirus as a model, we provide evidence to conclude that epitope hierarchy reflects competition on the level of antigen recognition. Notably, high-avidity cells specific for non-IDEs were found to expand only when IDEs were deleted. This may be a host’s back-up strategy to avoid viral immune escape through antigenic drift caused by IDE mutations. Importantly, our results are relevant for the design of vaccines based on cytomegaloviruses as vectors to generate high-avidity CD8+ T-cell memory specific for unrelated pathogens or tumors. We propose the deletion of vector-encoded IDEs to avoid the suppression of epitopes of the vaccine target.


2021 ◽  
Vol 6 (3) ◽  
pp. 121
Author(s):  
Alison Luce-Fedrow ◽  
Suchismita Chattopadhyay ◽  
Teik-Chye Chan ◽  
Gregory Pearson ◽  
John B. Patton ◽  
...  

The antigenic diversity of Orientia tsutsugamushi as well as the interstrain difference(s) associated with virulence in mice impose the necessity to dissect the host immune response. In this study we compared the host response in lethal and non-lethal murine models of O. tsutsugamushi infection using the two strains, Karp (New Guinea) and Woods (Australia). The models included the lethal model: Karp intraperitoneal (IP) challenge; and the nonlethal models: Karp intradermal (ID), Woods IP, and Woods ID challenges. We monitored bacterial trafficking to the liver, lung, spleen, kidney, heart, and blood, and seroconversion during the 21-day challenge. Bacterial trafficking to all organs was observed in both the lethal and nonlethal models of infection, with significant increases in average bacterial loads observed in the livers and hearts of the lethal model. Multicolor flow cytometry was utilized to analyze the CD4+ and CD8+ T cell populations and their intracellular production of the cytokines IFNγ, TNF, and IL2 (single, double, and triple combinations) associated with both the lethal and nonlethal murine models of infection. The lethal model was defined by a cytokine signature of double- (IFNγ-IL2) and triple-producing (IL2-TNF-IFNγ) CD4+ T-cell populations; no multifunctional signature was identified in the CD8+ T-cell populations associated with the lethal model. In the nonlethal model, the cytokine signature was predominated by CD4+ and CD8+ T-cell populations associated with single (IL2) and/or double (IL2-TNF) populations of producers. The cytokine signatures associated with our lethal model will become depletion targets in future experiments; those signatures associated with our nonlethal model are hypothesized to be related to the protective nature of the nonlethal challenges.


2006 ◽  
Vol 177 (1) ◽  
pp. 450-458 ◽  
Author(s):  
Michael W. Munks ◽  
Kathy S. Cho ◽  
Amelia K. Pinto ◽  
Sophie Sierro ◽  
Paul Klenerman ◽  
...  

JCI Insight ◽  
2018 ◽  
Vol 3 (19) ◽  
Author(s):  
Annemieke de Jong ◽  
Ali Jabbari ◽  
Zhenpeng Dai ◽  
Luzhou Xing ◽  
Dustin Lee ◽  
...  

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