# Acute Kidney Injury and Double Negative T Cells

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $516,264

## Abstract

Project Summary
Acute kidney injury (AKI) is associated with high mortality in native kidneys, decreased allograft survival in
transplants, and very high health care cost. Among the most common etiologies of AKI in both native and
transplanted kidneys is ischemia-reperfusion injury (IRI). There is currently no specific therapy for AKI and the
recovery process is incompletely understood. A major unknown is precise roles of each T cell type. This is
important as some T cells are involved in causing AKI, whereas others are involved in preventing tissue
damage and improving repair. Our team is focusing on characterizing and understanding the role of double
negative (DN)  T cells in healthy kidney and during AKI. DN T cells are one of the least understood T cell
types because of their paucity in peripheral lymphoid organs and thus have been relatively ignored. However,
we recently discovered DNT cells as a large constituent of kidney αβT cells (hereafter referred to as KDNT
cells). Significance of KDNT cells is underscored by their proven suppressive functions in vitro and
immunoregulatory protective function during experimental AKI. This renewal application is based on strong
recently published and unpublished preliminary data showing that KDNT cells are divided into two (PD-1+ and
NK1.1+) subsets in murine and human kidney. Murine PD-1+ DNT cells are actively dividing in the steady state
that is accompanied by a proliferative burst in response to experimental IRI by mechanisms that are not
restricted by known classical or non-classical MHC I and II molecules. The non-dividing NK1.1+ subset is
regulated by 2m-dependent non-classical MHC class I in mice. The major goals of this renewal application
are to investigate the regulatory role of PD-1 molecule, relationship of KDNT cells and renal tubular epithelial
cells (RTEC) in health and AKI, and translational of our murine findings to humans using human kidney
samples and from discarded deceased donors. Our specific Aims: Test the hypothesis that PD-1/PD-L system
regulates homeostasis and effector function of kidney DN T cells in health and AKI. 2) Test the hypothesis that
kidney DN and TREC regulate each other via a bidirectional loop during health and AKI. 3) Test the hypothesis
that human KDNT cells are suppresser cells that regulate homeostasis of RTEC during health and AKI. We
have all the key critical elements to achieve these goals that include an in vitro KDNT/RTEC culture system,
unique access to human kidney samples pre and post ischemia (from nephrectomies) and discarded deceased
donor kidneys, and a synergistic team of investigators with an established collaborative track record and
complementary expertise needed for successful outcome.

## Key facts

- **NIH application ID:** 9971179
- **Project number:** 2R01DK104662-06
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Abdel Rahim Hamad
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $516,264
- **Award type:** 2
- **Project period:** 2015-03-01 → 2024-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971179

## Citation

> US National Institutes of Health, RePORTER application 9971179, Acute Kidney Injury and Double Negative T Cells (2R01DK104662-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9971179. Licensed CC0.

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