# T cell Contributions to Neointima Formation in Pulmonary Hypertension

> **NIH HL K08** · STANFORD UNIVERSITY · 2026 · $165,888

## Abstract

Pulmonary Hypertension (PH) is a fatal disease where abnormal cells termed “neointima” progressively
occlude the pulmonary arteries leading to debilitating right heart failure. PH pathology is characterized by
perivascular inflammation, including T cell rich Tertiary Lymphoid Follicles (TLFs). Although perivascular
inflammation associates with worse outcomes, preclinical studies implicate T cells as having both pathogenic
and protective roles in PH. A repertoire of helper (Th) and regulatory (TReg) T cells shape the immune response
by sensing antigen via their T cell Receptors (TCRs) and clonally expanding in response. Current PH
therapies do not target neointima or inflammation. Lung transplant remains the only curative therapy. There is
a critical unmet need to understand how proliferating T cell lineages and their expressed ligands contribute to
neointima development in PH. Here, a mouse model of PH has been developed where human-like perivascular
inflammation, including TLFs form alongside occlusive neointimal lesions following chronic intranasal antigen
administration. Preliminary data finds that neointima and TLF formation is both T cell and antigen dependent.
Ablation of Tregs accelerates neointima formation and implicates a Th17 response. A single cell RNA
sequencing “Interactome Map” between T and vascular cells identifies Lymphotoxin (Ltb) as a major T cell-
vascular signal. Ltb expression is validated in human PH and Ltb blockade halts neointima and TLF formation
in mice. Using bulk and single cell TCR sequencing, the development of neointima formation associates with
the growth and suppression of T cell clones responding to antigens. The proposals central hypothesis is
neointima development in PH is dependent on a repertoire of pathogenic Cd4+ Th cell clones and the
pathogenicity of these clones is mediated by T cell expressed ligands, including Ltb. To test this, three Aims
are proposed: (1) Determine the Th cell sub-lineages responsible for pulmonary v

## Key facts

- **NIH application ID:** 11282978
- **Project number:** 1K08HL183852-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Adam Michael Andruska
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** HL
- **Fiscal year:** 2026
- **Award amount:** $165,888
- **Award type:** 1
- **Project period:** 2026-04-15T00:00:00 → 2031-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11282978

## Citation

> US National Institutes of Health, RePORTER application 11282978, T cell Contributions to Neointima Formation in Pulmonary Hypertension (1K08HL183852-01). Retrieved via AI Analytics 2026-06-30 from https://api.ai-analytics.org/grant/nih/11282978. Licensed CC0.

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