# Biology of human cytotoxic CD4 T cells (CD4-CTLs) in viral infections

> **NIH NIH U19** · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2023 · $698,113

## Abstract

PROJECT SUMMARY
Project 3
The existence of MHC class II-restricted CD4+ helper T cells with cytotoxic potential (CD4-CTLs) has been 
reported in humans with several viral infections. Importantly, the CD4-CTLs have been reported to play a 
protective role in several of these viral infections. However, little is known in humans about the biology of CD4-
CTL generation and their functional properties. We recently performed single-cell RNA-seq in over 9000 cells 
to unravel CD4-CTL heterogeneity and functional properties. Our analysis led to the discovery of a distinct 
subset of long-lived CD4-CTL memory precursors. Understanding the biology of such long-lived CD4-CTL 
precursors will pave the way for developing strategies to boost durable CD4-CTL immune responses following 
vaccination against infections. In Project 3, specific aim 1, we will determine the phenotype and functional 
properties of pathogen-specific and tissue-specific CD4-CTLs in humans. (A) Pathogen-specific features of 
CD4-CTLs: We will compare the phenotype and molecular features of circulating DENV-, hCMV-, EBV-reactive 
CD4-CTL precursors and effector cells. (B) Tissue-specific features of CD4-CTLs: Here, we will compare 
hCMV-, EBV- and pertussis vaccine-reactive CD4-CTLs present in human lungs to those circulating in the 
blood. In addition, we will compare pathogen-specific CD4-CTLs present in tonsil (lymphoid) tissue vs. blood 
(collaboration with Crotty, Project 1). (C) Vaccine-induced CD4-CTLs: In collaboration with Crotty (Project 1), 
we will determine whether yellow fever vaccination induces the generation of CD4-CTL precursors in the blood 
and lymph nodes. In specific aim 2, (A) we will identify molecular transcription factors driving CD4-CTL 
differentiation and (B) test their function in in vivo models and in human cells. In summary, our work will 
fundamentally advance our understanding of the molecular basis of CD4-CTL immunity in humans and will 
benefit from the synergistic interactions with other Projects.

## Key facts

- **NIH application ID:** 10580761
- **Project number:** 5U19AI142742-05
- **Recipient organization:** LA JOLLA INSTITUTE FOR IMMUNOLOGY
- **Principal Investigator:** Pandurangan Vijayanand
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $698,113
- **Award type:** 5
- **Project period:** 2019-03-11 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10580761

## Citation

> US National Institutes of Health, RePORTER application 10580761, Biology of human cytotoxic CD4 T cells (CD4-CTLs) in viral infections (5U19AI142742-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10580761. Licensed CC0.

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