# Induction of effector lymphocyte lethargy by helminth coinfection

> **NIH NIH R01** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2021 · $587,042

## Abstract

Abstract:
Helminth infections occur in populations worldwide and potentially modulate the immune
response to unrelated pathogens. An important consideration in the field is that
concomitant helminth infection could decrease the efficacy of vaccines. It is not known
how helminth infection impacts the formation and function of effector cells. Using an
ecologically appropriate model of mouse coinfection with H. polygyrus and vaccination
with T. gondii, we find that helminth infection inhibited the differentiation of effector CD8
T cells. Furthermore, the effector CTLs that develop in coinfected mice exhibit an
“lethargic” phenotype, marked by a deficiency in Tfb1m and depressed mitochondrial
biogenesis and defective effector cytokine response. Defective CD8 T cell differentiation
was associated also associated with an upregulation of Spry2, a negative regulator of
receptor signaling. Induction of defective effector differentiation by helminth coinfection
was mediated by host IL-4 and IL-10. To advance mechanistic understanding of helminth
induced effector lymphocyte lethargy, we propose three specific aims. In Aim 1, we will
leverage our recently developed technical advances and insights to delineate how
helminth coinfection negatively impacts CD8 T cell activation, proliferation and
differentiation. In Aim2, we will interrogate the functional role of mitochondrial insufficiency
in helminth-induced effector dysfunction. Finally, in Aim 3, we will dissect the role of Spry2
and CD8 T cell intrinsic IL4 and IL-10 signaling in helminth-induced lymphocyte lethargy.
Together, these studies will advance mechanistic understanding of effector cell
dysfunction and provide avenues for therapeutic reversal.
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## Key facts

- **NIH application ID:** 10140288
- **Project number:** 5R01AI134040-05
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** William Clark Gause
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $587,042
- **Award type:** 5
- **Project period:** 2017-05-19 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10140288

## Citation

> US National Institutes of Health, RePORTER application 10140288, Induction of effector lymphocyte lethargy by helminth coinfection (5R01AI134040-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10140288. Licensed CC0.

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