# Intravascular Immune Surveillance by Anti-viral T Cells

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2024 · $637,862

## Abstract

CD8 T cells mediate adaptive immune responses against malignant tumors and intracellular
pathogens. In order to exert their protective effector functions, they must engage in physical
contacts with their targets. Thus, T cells migrate actively within the body in search of cognate
antigens. Following encounter of viral antigens, anti-viral T cells make a series of fate decisions
that determine their differentiation into phenotypically diverse effector (Teff) and memory cell
(Tmem) subsets that possess specialized properties. The rules that govern the magnitude,
functional differentiation, migratory properties and life-span of virus-specific T cell subsets are
incompletely understood. Recent work has shown that the chemokine receptor CX3CR1
identifies three distinct CD8+ Teff and Tmem subsets that are induced by systemic viral infections.
The largest subset expresses high levels of CX3CR1 and is permanently devoid of lymph node
homing receptors. Consequently, CX3CR1hi Teff and Tmem (referred to as effector memory cells,
or Tem) are abundant in blood and spleen, but absent from other lymphoid tissues. Contrary to
the prevailing paradigm, preliminary experiments indicate that CX3CR1hi Teff and Tem are also
excluded from the extravascular compartment in non-lymphoid tissues. Instead, multi-photon
intravital microscopy observations indicate that large numbers of CX3CR1hi T cells marginate
and arrest within venules and then crawl against the blood stream across the capillary bed into
arterioles where the CX3CR1hi T cells are found at high density. The present project will explore
the hypothesis that crawling Teff and Tem employ unique molecular mechanisms to adhere and
migrate within the microvasculature to survey microvascular endothelial cells for antigens and to
receive signals that shape the Tmem repertoire. This hypothesis will be addressed in two specific
aims: (1.) to characterize the migratory properties of intravascular anti-viral Teff and Tmem; and
(2.) to assess the impact of intravascular T cell crawling on Teff and Tmem differentiation and
function.

## Key facts

- **NIH application ID:** 10728876
- **Project number:** 5R01AI155865-04
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** ULRICH H VON ANDRIAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $637,862
- **Award type:** 5
- **Project period:** 2020-11-17 → 2025-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10728876

## Citation

> US National Institutes of Health, RePORTER application 10728876, Intravascular Immune Surveillance by Anti-viral T Cells (5R01AI155865-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10728876. Licensed CC0.

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