# Effects of Memory T Cells on the Response to Cecal Ligation and Puncture

> **NIH NIH K08** · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · 2021 · $195,480

## Abstract

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. The immune
system plays a central role in this dysregulated host response; immune abnormalities have been identified in
clinical sepsis and in murine cecal ligation and puncture (CLP), the most widely-used animal model of sepsis.
However, the effect of a significant aspect of the immune response, the memory T cell response, has escaped
investigation in the CLP model. Recent studies have demonstrated that laboratory mice lack a well-developed
repertoire of memory T cells, a deficiency not present in mice “in the wild” – or in patients with sepsis. Thus, the
contribution of this vital component of adaptive immunity is unknown. This gap in our understanding of the role
of memory T cell populations in CLP assumes even greater importance considering reports that immune
responses to sub-lethal infections in laboratory mice and “wild” mice differed substantially. Therefore, we
undertook preliminary studies to determine if lack of this memory T cell component substantially effects
responses to CLP. To induce a robust memory T cell repertoire, we treated C57Bl6 mice with an activating
antibody to CD3ε, activating a diverse repertoire of T cells and inducing both CD4 and CD8 T cell memory while
decreasing naïve T cell proportions without altering total T cell numbers. These “immune educated” mice
(following a 35 day rest) respond quite differently to CLP when challenged, with an increased numbers of IFNɣ-
producing CD4 T cells and a decreased numbers of TNFα producing CD8 T cells. Other changes seen in educated
mice included increased neutrophil infiltration into the liver and enhancement of monocyte function.
Importantly, CLP in educated mice was also associated with altered liver function, bacterial clearance, and weight
loss. These findings lead to our global hypothesis: immune education alters the effects of CLP on
organ function, innate immunity and outcomes. We will test this hypothesis via through comparison of
immune educated mice treated with the anti-CD3ε antibody to naïve mice following CLP. We will initially identify
variation in physiologic presentation and parameters of organ dysfunction and clinical outcomes along with
differences in the immune response to CLP in both the innate and adaptive immune response. Once we have
identified specific variations, we will determine causative T cell populations through specific T cell knockouts
along with adoptive transfer experiments of memory and naïve T cells. Furthermore, we will collect peripheral
blood samples from septic patients and healthy control patients and examine memory T cell populations and
innate immune cell function in sepsis. Ultimately, these experiments will demonstrate the role of memory T cells
in CLP and the septic immune response. Moreover, determination of this role may offer potential novel therapies
for sepsis and perhaps other severe infectious or inflammatory disorders.

## Key facts

- **NIH application ID:** 10149348
- **Project number:** 5K08GM132794-03
- **Recipient organization:** FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** Matthew David Taylor
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $195,480
- **Award type:** 5
- **Project period:** 2019-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10149348

## Citation

> US National Institutes of Health, RePORTER application 10149348, Effects of Memory T Cells on the Response to Cecal Ligation and Puncture (5K08GM132794-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10149348. Licensed CC0.

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