Distinct transcriptomic signatures in pulmonary tissue resident and vascular resident-like T cells in nonhuman primates
The concept of intravascular immunity is reshaping our understanding of immune surveillance, challenging the traditional view that immune responses are confined to either tissue parenchyma or the bloodstream. Our pilot study utilized intravascular staining (ivs) in rhesus macaques (RhM) to spatially distinguish pulmonary vasculature-associated (ivs+) CD8<sup>+</sup> T cells from interstitial (ivs-) T cells. Single-cell RNA sequencing and flow cytometry revealed that ivs+ T cells are not passive blood contaminants but rather a distinct, "resident-like" population enriched in cytotoxic effectors, with elevated expression of transcripts associated with tissue residency, cell adhesion, and vascular/platelet interactions, while ivs- T cells exhibited a classic T<sub>RM</sub> signature. The presence of SIV-specific tetramer+ ivs+ CD8<sup>+</sup> T cells in infected RhM suggests a role in antiviral defense within the lung vasculature. These findings provide new insight into intravascular immunity, highlighting a unique population of CD8<sup>+</sup> T cells as potential pulmonary vascular sentinels poised for rapid immune responses.
Authors
- Alexandra Melton (ORCID: https://orcid.org/0000-0002-1671-2905)
- Sarah E. Scheuermann (ORCID: https://orcid.org/0000-0002-9899-997X)
- E. Lake Potter
- Toni Penney (ORCID: https://orcid.org/0000-0002-1571-2006)
- Kasi Russell‐Lodrigue (ORCID: https://orcid.org/0000-0003-3719-0779)
- Lori A. Rowe (ORCID: https://orcid.org/0000-0003-3744-496X)
- Robert V. Blair (ORCID: https://orcid.org/0000-0001-9616-9414)
- Jay K. Kolls (ORCID: https://orcid.org/0000-0001-5151-6304)
- Diogo M. Magnani (ORCID: https://orcid.org/0000-0002-1773-2406)
- Nicholas J. Maness (ORCID: https://orcid.org/0000-0002-9332-7891)
- Hunter J. Melton (ORCID: https://orcid.org/0000-0002-8692-7178)
- Kelly Goff (ORCID: https://orcid.org/0000-0003-2682-6532)
- Clara Krzykwa (ORCID: https://orcid.org/0009-0003-7873-1444)
Institutions
- Dartmouth College (US)
- Tulane University (US)
- National Institutes of Health (US)
- University of Massachusetts Chan Medical School (US)
- National Institute of Allergy and Infectious Diseases (US)
Publication Details
- Journal
- iScience
- Published
- 2025-05-26
- DOI
- https://doi.org/10.1016/j.isci.2025.112745
- Citations
- 2
- Primary Topic
- Atherosclerosis and Cardiovascular Diseases
- Type
- article
- Field-Weighted Citation Impact
- 1.59
Funders
- Gilead Sciences
- National Institutes of Health
- National Heart, Lung, and Blood Institute
- NIH Office of the Director
- National Institute of Allergy and Infectious Diseases