# Expanded Double Negative T cells in SLE.

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2024 · $497,839

## Abstract

Systemic lupus erythematosus afflicts 1 to 2 million Americans and is associated with significant
morbidity and mortality. While wiser use of immunosuppressive drugs and prompt treatment of
complications have improved the overall survival and quality of life, we still lack specific drugs,
full understanding of the involved pathogenic processes and valuable disease biomarkers. In
addition, our understanding of local, organ-specific mechanisms involved in the execution of
tissue injury is limited. An expanded population of T cells missing CD4 and CD8 from the
surface (double negative T cells) in the peripheral blood of patients with systemic lupus
erythematosus, helps autologous B cells to produce immunoglobulin and dsDNA antibodies,
produces the proinflammatory interleukin 17 and invades tissues to cause inflammation. This
application proposes the use of state-of-the-art new technologies including spectral cytometry,
single cell RNA sequencing and series of novel engineered mice to study the diversity of the
double negative T cell population in the peripheral blood and kidneys of lupus-prone mice and
people with systemic lupus erythematosus and understand how an inflammatory environment
contributes to their generation. In parallel, experiments are proposed to understand how
inflammatory cytokines act on kidney resident cells to enable the establishment of inflammation.
The proposed experiments will inform the development of approaches to suppress the
generation of pathogenic double negative T cells and prevent the establishment of tissue
inflammation.

## Key facts

- **NIH application ID:** 10842233
- **Project number:** 5R01AI085567-14
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** George C Tsokos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $497,839
- **Award type:** 5
- **Project period:** 2010-05-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842233

## Citation

> US National Institutes of Health, RePORTER application 10842233, Expanded Double Negative T cells in SLE. (5R01AI085567-14). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10842233. Licensed CC0.

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