# T cells in Lupus

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2022 · $437,500

## Abstract

The multitude of mechanisms that lead to general break of tolerance and organ pathology in
patients with systemic lupus erythematosus (SLE) have challenged both basic immunologists
and translational researchers. Infections remain one of the main causes of morbidity and
mortality among patients with SLE despite our significantly improved ability to diagnose and
treat infections early and efficiently.
Search for genes expressed in T cells from patients with SLE revealed CD38 to be associated
with more severe disease and extensive aberrant gene expression. CD8+CD38+ T cells were
found expanded in patients with SLE and to be strongly associated with increased infection
rates. CD8+CD38+ cells display compromised cytotoxic activity, less amounts of nicotinamide
adenine dinucleotide (NAD+), decreased glycolysis and oxidative phosphorylation and
decreased expression of molecules responsible for the performance of cytotoxic cell function.
In addition, inhibition of CD38 appeared to restore aspects of cytotoxic cell function.
The hypothesis which will guide the proposed studies is: increased expression of CD38 on
CD8+ cells in patients with SLE and lupus-prone mice compromises their cytotoxic activity and
predisposes to infections and drives autoimmunity. Three sets of experiments using human cells
and novel mice will be conducted to test the hypothesis. The first will determine how CD38
expression limits cytotoxicity in CD8 cells. The second will explore approaches to enhance
cytotoxic responses of SLE CD8+ cells including targeted delivery of drugs to T cells. Whereas,
in the third we will conduct a pilot prospective study to determine the value of CD38 expression
in identifying patients with SLE prone to infections.
The identification of the CD8+CD38+ T cell subset to be expanded in SLE patients and role of
CD38 in limiting their cytotoxic activity along with the design of new mice represent novel
concepts in the field of lupus. The search for approaches to restore their cytotoxic activity and
the clinical study to define them as a biomarker for SLE patients prone to infections represent
the translational value of this line of research.

## Key facts

- **NIH application ID:** 10308697
- **Project number:** 5R01AI148161-03
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** George C Tsokos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $437,500
- **Award type:** 5
- **Project period:** 2019-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10308697

## Citation

> US National Institutes of Health, RePORTER application 10308697, T cells in Lupus (5R01AI148161-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10308697. Licensed CC0.

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