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Lung Resident Memory T Cells Activated by Oral Vaccination Afford Comprehensive Protection against Pneumonic Yersinia pestis Infection - The Journal o

Mary Wilson

Well-known member
DECEMBER 07 2022

https://doi.org/10.4049/jimmunol.2200487

Amit K. Singh; Saugata Majumder; Xiuran Wang; Renjie Song; Wei Sun

Abstract

A growing body of evidence has shown that resident memory T (T[SUB]RM[/SUB]) cells formed in tissue after mucosal infection or vaccination are crucial for counteracting reinfection by pathogens. However, whether lung T[SUB]RM[/SUB] cells activated by oral immunization with Yptb1(pYA5199) play a protective role against pneumonic plague remains unclear. In this study, we demonstrated that lung CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T[SUB]RM[/SUB] cells significantly accumulated in the lungs of orally Yptb1(pYA5199)-vaccinated mice and dramatically expanded with elevated IL-17A, IFN-γ, and/or TNF-α production after pulmonary Yersinia pestis infection and afforded significant protection. Short-term or long-term treatment of immunized mice with FTY720 did not affect lung T[SUB]RM[/SUB] cell formation and expansion or protection against pneumonic plague. Moreover, the intratracheal transfer of both lung CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T[SUB]RM[/SUB] cells conferred comprehensive protection against pneumonic plague in naive recipient mice. Lung T[SUB]RM[/SUB] cell–mediated protection was dramatically abolished by the neutralization of both IFN-γ and IL-17A. Our findings reveal that lung T[SUB]RM[/SUB] cells can be activated via oral Yptb1(pYA5199) vaccination, and that IL-17A and IFN-γ production play an essential role in adaptive immunity against pulmonary Y. pestis infection. This study highlights an important new target for developing an effective pneumonic plague vaccine.

https://watermark.silverchair.com/j...y2g6dpHWjh4LBcj9f0zwPUVQF2UST5xj5RHw7kpumjX0k
 
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