Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Παρασκευή 18 Νοεμβρίου 2016

Acute Virus Control Mediated by Licensed NK Cells Sets Primary CD8+ T Cell Dependence on CD27 Costimulation [INFECTIOUS DISEASE AND HOST RESPONSE]

NK cells represent a critical first-line of immune defense against a bevy of viral pathogens, and infection can provoke them to mediate supportive and suppressive effects on virus-specific adaptive immunity. In mice expressing MHC class I Dk (Dk), a major murine CMV (MCMV) resistance factor and self-ligand of the inhibitory Ly49G2 (G2) receptor, licensed G2+ NK cells provide essential host resistance against MCMV infection. Additionally G2+ NK cell responses to MCMV increase the rate and extent of dendritic cell (DC) recovery, as well as early priming of CD8+ T cell effectors in response to MCMV. However, relatively little is known about the NK cell effect on costimulatory ligand patterns displayed by DCs or on ensuing effector and memory T cell responses. In this study, we found that CD27-dependent CD8+ T cell priming and differentiation are shaped by the efficiency of NK responses to virus infection. Surprisingly, differences in specific NK responses to MCMV in Dk-disparate mice failed to distinguish early DC costimulatory patterns. Nonetheless, although CD27 deficiency did not impede licensed NK-mediated resistance, CD70 and CD27 were required to efficiently prime and regulate effector CD8+ T cell differentiation in response to MCMV, which eventually resulted in biased memory T cell precursor formation in Dk mice. In contrast, CD8+ T cells accrued more slowly in non-Dk mice and eventually differentiated into terminal effector cells regardless of CD27 stimulation. Disparity in this requirement for CD27 signaling indicates that specific virus control mediated by NK cells can shape DC costimulatory signals needed to prime CD8+ T cells and eventual T cell fate decisions.



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