Pitt Pediatrics congratulates John Williams, MD, for his recent publication in Immunohorizons, titled “PD-1 Impairs CD8+ T Cell Granzyme B Production in Aged Mice during Acute Viral Respiratory Infection.” Williams is the Henry L. Hillman Professor of Pediatric Immunology, Director of the Division of Infectious Disease, and the Director of the Institute for Infection, Inflammation, and Immunity for Children (i4Kids). 
Other contributors to this article include MD/PhD student Olivia Parks as first author, as well as Sara Walters, MS and Monika Johnson, all of the Division of Infectious Disease. Other co-authors include Danielle Antos (Div. of Pulmonology), Taylor Eddens, MD (Div. of Allergy/Immunology), Tim D. Oury, MD, PhD (Pathology), and Rachel A. Gottschalk, PhD, (Immunology).
This research looks specifically at CD8+ T cells, which are the primary cell type responsible for viral clearance. However, as cell function declines over time and in conjunction with an accumulation of cytotoxic tissue-resident memory (TRM) CD8+ T cells, they can also contribute to severe respiratory viral infection outcomes in older adults.
The research team therefore aimed to clarify the role PD-1 signaling has on aged CD8+ T cell function during acute viral respiratory tract infection, as PD-1 is significant in the regulation of CD8+ T cells during infection. Observations revealed that PD-1 blockade in aged mice yielded healthy CD8+ T cell production to comparable levels in young mice during viral infections. Further investigation demonstrated syngeneic transplant and adoptive transfer strategies improved healthy production even within cells transplanted from aged hosts into younger ones. This indicated that healthy production is cell-intrinsic, and can be associated with PD-1 signaling in various host ages.
Ultimately, Williams and the research team later observed that PD-1 blockade of aged mice during re-infection resulted in improved clinical outcomes similar to the effect of reduced levels of CD8+ TRM cells. These findings therefore implies that PD-1 checkpoint inhibitors may be a potential therapeutic option for elderly patients with severe respiratory viral infections.
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