TY - JOUR

T1 - Prevention of respiratory virus transmission by resident memory CD8 + T cells.

AU - Uddbäck, Ida

AU - Michalets, Sarah E

AU - Saha, Ananya

AU - Mattingly, Cameron

AU - Kost, Kirsten N

AU - Williams, M Elliott

AU - Lawrence, Laurel A

AU - Hicks, Sakeenah L

AU - Lowen, Anice C

AU - Ahmed, Hasan

AU - Thomsen, Allan R

AU - Russell, Charles J

AU - Scharer, Christopher D

AU - Boss, Jeremy M

AU - Koelle, Katia

AU - Antia, Rustom

AU - Christensen, Jan P

AU - Kohlmeier, Jacob E

N1 - © 2023. The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2024

Y1 - 2024

N2 - An ideal vaccine not only attenuates virus growth and disease in infected individuals but also reduces the spread of infections in the population, thereby generating herd immunity. While this strategy has proven successful by generating humoral immunity to measles, yellow fever and polio, many respiratory viruses evolve to evade pre-existing antibodies 1. One approach for improving the breadth of antiviral immunity against escape variants is through the generation of memory T cells in the respiratory tract, which are positioned to rapidly respond to respiratory virus infections 2-6. However, it is unknown whether memory T cells alone can effectively surveil the respiratory tract to an extent that they eliminate or greatly reduce viral transmission following exposure of an individual to infection. Here, we use a mouse model of natural parainfluenza virus transmission to quantify the extent to which memory CD8 T cells resident in the respiratory tract can provide herd immunity by reducing both the susceptibility of acquiring infection and the extent of transmission, even in the absence of virus-specific antibodies. We demonstrate that protection by resident memory CD8 T cells requires the antiviral cytokine IFN-γ and leads to altered transcriptional programming of epithelial cells within the respiratory tract. These results suggest that tissue-resident CD8 T cells in the respiratory tract can play important roles in both protecting the host against viral disease and in limiting viral spread throughout the population.

AB - An ideal vaccine not only attenuates virus growth and disease in infected individuals but also reduces the spread of infections in the population, thereby generating herd immunity. While this strategy has proven successful by generating humoral immunity to measles, yellow fever and polio, many respiratory viruses evolve to evade pre-existing antibodies 1. One approach for improving the breadth of antiviral immunity against escape variants is through the generation of memory T cells in the respiratory tract, which are positioned to rapidly respond to respiratory virus infections 2-6. However, it is unknown whether memory T cells alone can effectively surveil the respiratory tract to an extent that they eliminate or greatly reduce viral transmission following exposure of an individual to infection. Here, we use a mouse model of natural parainfluenza virus transmission to quantify the extent to which memory CD8 T cells resident in the respiratory tract can provide herd immunity by reducing both the susceptibility of acquiring infection and the extent of transmission, even in the absence of virus-specific antibodies. We demonstrate that protection by resident memory CD8 T cells requires the antiviral cytokine IFN-γ and leads to altered transcriptional programming of epithelial cells within the respiratory tract. These results suggest that tissue-resident CD8 T cells in the respiratory tract can play important roles in both protecting the host against viral disease and in limiting viral spread throughout the population.

U2 - 10.1038/s41586-023-06937-1

DO - 10.1038/s41586-023-06937-1

M3 - Journal article

C2 - 38086420

VL - 626

SP - 392

EP - 400

JO - Nature

JF - Nature

SN - 0028-0836

ER -