# The role of early microbial exposure in the ontogeny of CD8+ T cells

> **NIH NIH F31** · CORNELL UNIVERSITY · 2022 · $1

## Abstract

Project Summary/Abstract
The amount of microbial exposure an individual experiences in utero and early in life has a lasting and profound
impact on their immune status later in life. A growing number of reports have associated exposure to a diverse
range of microbes with an enhanced immune response against unrelated pathogens. However, the mechanisms
in which the microbial environment shapes the development of the immune system is unknown. To provide
insight into this question, we modified the ‘pet-shop’ mouse model so that laboratory mice would be exposed to
pathogens for the entirety of their development. Interestingly, we found mice raised in a ‘dirty’ environment have
enhanced immune protection against intracellular infections, which was associated with changes in the CD8+ T
cell compartment. To understand how the CD8+ T cell compartment was altered in a ‘dirty’ environment, we
used our ‘timestamp’ mice and tracked the fates of T cells produced at different stages of life. We found that
increased resistance to intracellular pathogens was linked to a higher proportion of ‘fast-acting’ fetal-derived
CD8+ T cells and lower proportion of ‘slow-acting’ adult-derived CD8+ T cells present in adulthood. These data
suggests that microbial exposure in early life leads to permanent changes in the immune system by altering the
developmental layering of the peripheral T cell compartment. The main goal of this proposal is to identify the key
mechanisms that alter the developmental layering of CD8+ T cells in dirty mice. In aim 1, I will determine how
the production and maintenance of CD8+ T cells is altered in dirty mice. In aim 2, I will assess how cell-intrinsic
and environmental factors contribute to the altered composition of CD8+ T cells in dirty mice. This proposal aims
to create a conceptual framework to understand how microbial exposure in early life alters the development of
the CD8+ T cell compartment. Knowledge gained from this proposal has the potential to result in a paradigm
shift of how we understand immune ontogeny and immune cell instruction.

## Key facts

- **NIH application ID:** 10548112
- **Project number:** 5F31AI157236-02
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Cybelle Tabilas
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1
- **Award type:** 5
- **Project period:** 2021-09-16 → 2022-09-17

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10548112

## Citation

> US National Institutes of Health, RePORTER application 10548112, The role of early microbial exposure in the ontogeny of CD8+ T cells (5F31AI157236-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10548112. Licensed CC0.

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