# Role of PD1 blockade and IL-10 during infection in aging

> **NIH NIH R21** · UNIVERSITY OF MINNESOTA · 2022 · $226,113

## Abstract

PROJECT SUMMARY
The elderly are at high risk for mortality to infection, with influenza and pneumonia consistently ranked among
the top leading causes of death in the US for those over 65. There is also an increased rate of co-infections in
the elderly admitted to the ICU that is associated with hospital mortality. There is a need for novel approaches
that rejuvenate the aged immune system to promote the control of infection. We leverage an experimental
paradigm that exposes experimental mice to multiple microbes (termed normal microbial experience; NME).
NME activates the immune system in young mice, increasing functional memory T cells. However, in old mice,
NME-exposure leads to 100% mortality that is preceded by a cytokine storm and increased immune infiltrates
in multiple tissues. Existing evidence demonstrates that immunosenescence, including inflammaging and the
dysfunctional immune system, play a causal role in morbidity to infections in the elderly. Exhaustion is a cell
fate that is increased in lymphocytes from the elderly, and which contributes to inflammaging, virus
persistence, and tissue pathology. It is primarily enforced by chronic antigen exposure, but also regulated by
local secreted factors, like IL-10 in younger individuals. It is unknown how specific factors control exhaustion
prior to and during infection in older individuals. We speculate that IL-10, a traditional anti-inflammatory
cytokine that accumulates with age, and which also has pro-cytotoxic effects on CD8 T cells, is a regulator of
exhaustion with age. This proposal is based on our exciting preliminary data which describes the effect of PD1
blockade, which reduces exhaustion by restoring T cell activation and implicates IL-10 in that response. Based
on our data, we wonder: does IL-10 promotes exhaustion or prevents it? We hypothesize that PD1 blockade
relieves CD8+ T cell exhaustion in an IL-10/IL-10R dependent manner. We will use the experimental paradigm
of NME-exposure to test this hypothesis. Aim 1 is to establish the role for IL-10/IL-10R in supporting T cell
function during aging. Aim2 is to determine the mechanism by which IL-10 supports T cell function in aged
mice.

## Key facts

- **NIH application ID:** 10509657
- **Project number:** 1R21AG078638-01
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Christina Camell
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $226,113
- **Award type:** 1
- **Project period:** 2022-09-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10509657

## Citation

> US National Institutes of Health, RePORTER application 10509657, Role of PD1 blockade and IL-10 during infection in aging (1R21AG078638-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10509657. Licensed CC0.

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