# Translational Regulation of CD8 T-Cell Immunity - Transfer of R01AI139675 from Emory

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2022 · $454,637

## Abstract

CD8 T cells play an important role in controlling viral infections as well as intracellular bacterial and parasitic
infections. It is now clear that CD8 T cells are also involved in immunity against tumors and there is
considerable interest in cancer immunotherapy that stimulates CD8 T cell responses. Thus, understanding the
mechanisms that regulate antigen specific CD8 T cell responses is critical not only for the rational design of
vaccines but also for development of novel approaches to enhance CD8 T cells for immunotherapy. Genome-
wide transcriptional profiles of antigen specific CD8 T cells during acute infection have been extensively
studied to elucidate the molecular basis of differentiation process from naive to effector to memory T cells. One
of the interesting features obtained from such studies is downregulation of transcripts related to translation in
effector CD8 T cells compared to naive CD8 T cells. Similarly, transcriptional inhibition of mRNAs associated
with translation has been also observed in memory CD8 T cells repeatedly stimulated with multiple rounds of
acute infection. Furthermore, transcriptional downregulation of a group of mRNAs important for translation has
been reported in exhausted CD8 T cells that arose after chronic infection. These data strongly suggest that
translation plays an essential role in regulation of antigen specific CD8 T cell responses during acute and
chronic infections. However, translational control in antigen specific CD8 T cells in vivo has not been well
studied, and thus understanding translational regulation is a new frontier of research for CD8 T cell immunity.
We have recently tackled this important issue, and have shown that translation is actively regulated during the
differentiation of CD8 effector T cells. Based on our observations, we hypothesized that translation plays an
essential role in regulation of CD8 T cell responses and can be targeted to modulate CD8 T cell immunity. Our
proposed studies on understanding translational regulation of antigen specific CD8 T cell responses during
acute and chronic infections represent a new direction of research in the area of T cell memory and exhaustion.
These studies will also provide crucial information to enhance protective CD8 T cell immunity against
pathogens and viral-mediated cancers by targeting translational regulation. The following specific aims are
proposed: Specific Aim 1: To examine the role of eIF4E-dependent translation in the fate decisions involved in
the formation of terminal effector and memory precursor CD8 T cells during acute infection. Specific Aim 2: To
understand how translational regulation dependent on mTORC1-S6K-eIF4A signals regulates the fate of
effector CD8 T cell differentiation during acute infection. Specific Aim 3: To understand translational regulation
of CD8 T cell exhaustion during chronic infection.

## Key facts

- **NIH application ID:** 10451803
- **Project number:** 5R01AI139675-06
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Koichi Araki
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $454,637
- **Award type:** 5
- **Project period:** 2018-08-14 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10451803

## Citation

> US National Institutes of Health, RePORTER application 10451803, Translational Regulation of CD8 T-Cell Immunity - Transfer of R01AI139675 from Emory (5R01AI139675-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10451803. Licensed CC0.

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