# Cytotoxic CD4+ T cells and autoimmune fibrotic disorders

> **NIH NIH U19** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $252,000

## Abstract

PROJECT SUMMARY
This project focuses on the underlying basis of an autoimmune fibrotic disorder, IgG4-
related disease. We will use multi-color multispectral imaging of disease tissues, cell
distance mapping as well as single-cell transcriptomics to interrogate tissues from IgG4-
related disease. In particular we wish to identify and quantitate CD4+cytotoxic T cells
and activated B cell subsets and better understand whether they directly contribute to
cell death in tissues and thus to fibrosis, or if they primarily secrete fibrogenic products.
We also want to understand the molecular basis by which CD4+cytotoxic T cells
differentiate. We will test two competing but mutually non-exclusive hypotheses - one
that CD4+T cells, with the help of activated B cells drive tissue cell death as a prelude to
fibrosis, and the other that the cytokines and enzymes secreted by activated T cells and
disease-related B cells are causal for fibrosis. We will also examine the interactions
between adaptive and innate immune cells in disease and identify antigens that trigger
clonally expanded B and T cells in patients. We will also explore the possibility that
somatic mutations in hematopoietic stem cells or in CD4+CTL clones contribute to
disease pathogenesis.

## Key facts

- **NIH application ID:** 9915866
- **Project number:** 5U19AI110495-07
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** SHIV Subramaniam PILLAI
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $252,000
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9915866

## Citation

> US National Institutes of Health, RePORTER application 9915866, Cytotoxic CD4+ T cells and autoimmune fibrotic disorders (5U19AI110495-07). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/9915866. Licensed CC0.

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