Innate and Adaptive Immune Pathways to Tolerance

2009 ◽  
pp. 45-61 ◽  
Author(s):  
Catherine A. Thornton ◽  
Gareth Morgan
Keyword(s):  
Adaptive Immune ◽  
Immune Pathways

scholarly journals Sustained IL-15 response signature predicts RhCMV/SIV vaccine efficacy

2021 ◽  
Author(s):  
Fredrik Barrenäs ◽  
Scott G. Hansen ◽  
Lynn Law ◽  
Connor Driscoll ◽  
Richard R. Green ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Cell Function ◽  
Effector Memory ◽  
Highly Pathogenic ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Immune Pathways

AbstractSimian immunodeficiency virus (SIV) challenge of rhesus macaques (RMs) vaccinated with Rhesus Cytomegalovirus (RhCMV) vectors expressing SIV proteins (RhCMV/SIV) results in a binary outcome: stringent control and subsequent clearance of highly pathogenic SIV in ~55% of vaccinated RMs with no protection in the remaining 45%. Although previous work suggests that unconventionally restricted, SIV-specific, effector-memory (EM)-biased CD8+ T cell responses are necessary for efficacy, the magnitude of these responses does not predict efficacy, and the basis of protection vs. non-protection in RhCMV/SIV vector-vaccinated RMs has not been elucidated. Here, we report that RhCMV/SIV vector administration strikingly alters the whole blood transcriptome of vaccinated RMs, with the sustained induction of specific immune-related pathways, including non-canonical T cell receptor (TCR), toll-lie receptor (TLR), inflammasome/cell death, and interleukin-15 (IL-15) signaling, significantly predicting protection. The IL-15 gene expression signature was further evaluated in an independent RM IL-15 treatment cohort, revealing that in whole blood the response to IL-15 is inclusive of innate and adaptive immune gene expression networks that link with RhCMV/SIV vaccine efficacy. We also show that this IL-15 response signature similarly tracks with vaccine protection in an independent RhCMV/SIV vaccination/SIV challenge RM validation cohort. Thus, the RhCMV/SIV vaccine imparts a coordinated and persistent induction of innate and adaptive immune pathways featuring IL-15, a known regulator of CD8+ T cell function, that enable vaccine-elicited CD8+ T cells to mediate protection against highly pathogenic SIV challenge.Author SummarySIV insert-expressing vaccine vectors based on strain 68-1 RhCMV elicit robust, highly effector-memory-biased T cell responses that are associated with an unprecedented level of SIV control after challenge (replication arrest leading to clearance) in slightly over half of vaccinated monkeys. Since efficacy is not predicted by standard measures of immunogenicity, we used functional genomics analysis of RhCMV/SIV vaccinated monkeys with known challenge outcomes to identify immune correlates of protection. We found that arrest of viral replication after challenge significantly correlates with a vaccine-induced response to IL-15 that includes modulation of T cell, inflammation, TLR signaling, and cell death programming. These data suggest that RhCMV/SIV efficacy is not based on chance, but rather, results from a coordinated and sustained vaccine-mediated induction of innate and adaptive immune pathways featuring IL-15, a known regulator of CD8+ effector-memory T cell function, that enable vaccine-elicited CD8+ T cells to mediate efficacy.

scholarly journals Su1803 – Tweak/Fn14 Ameliorates Experimental Ileitis by Regulating Critical Innate and Adaptive Immune Pathways in Samp1/Yitfc Mouse Model

2019 ◽  
Vol 156 (6) ◽  
pp. S-618
Author(s):  
Luca Di Martino ◽  
Fabio Cominelli ◽  
Theresa T. Pizarro ◽  
Abdullah Osme
Keyword(s):  
Mouse Model ◽  
Adaptive Immune ◽  
Immune Pathways

scholarly journals TWEAK/Fn14 Is Overexpressed in Crohn’s Disease and Mediates Experimental Ileitis by Regulating Critical Innate and Adaptive Immune Pathways

2019 ◽  
Vol 8 (3) ◽  
pp. 427-446 ◽  
Author(s):  
Luca Di Martino ◽  
Abdullah Osme ◽  
Sarah Kossak-Gupta ◽  
Theresa T. Pizarro ◽  
Fabio Cominelli
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adaptive Immune ◽  
Immune Pathways
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