Kidney Double Negative TCR αβ + Cells: Newly Described Intra-Renal Kidney Lymphocytes That Respond to Ischemia Reperfusion in Mice
1Pathology, Johns Hopkins University, Baltimore, MD
2Medicine, Johns Hopkins University, Baltimore, MD.
Meeting: 2015 American Transplant Congress
Abstract number: 186
Keywords: Inflammation, Ischemia, Kidney transplantation, Lymphocytes
Session Information
Session Name: Concurrent Session: Ischemia Reperfusion Injury: Basic Mechanisms
Session Type: Concurrent Session
Date: Monday, May 4, 2015
Session Time: 2:15pm-3:45pm
Presentation Time: 2:27pm-2:39pm
Location: Room 119-A
Background TCRαβ+CD4-CD8- double negative (DN) T cells with immunoregulatory function are a significant component of T cells residing in the kidney. The exact role of DN T cells in renal immune cell homeostasis in the steady state and after transplantation is not known. In this study we have explored the functional role of DNT cells in mouse kidney under steady state condition and following ischemia reperfusion injury (IRI).
Methods CD45+ lymphocytes were purified from kidney mononuclear cells isolated from normal and post ischemic kidneys and were analyzed for activation marker and co-stimulatory molecules by flow cytometry. Microarray analysis of flow sorted DNT cells was performed to decipher unique genomic signatures in DN T cells distinct from CD4 and CD8 cells. Adoptive transfer experiment was performed to further clarify the immune function of DNT cells during IRI. Furthermore, we measured intracellular cytokines in the kidney lymphocyte.
Findings The frequency of DN T cells in the kidney was higher than other T cell subsets at baseline (30%) and 3 hours post IRI (>60%). DNT also showed an activated phenotype indicated by high expression of CD40L, CD28 co-stimulatory molecules and activation marker CD69. DN T cells proliferate at a very high rate in normal kidney (30% BrdU incorporation) with further increase in proliferation after IRI (80% BrdU incorporation). Adoptive transfer of DN T cells 3h prior to IRI resulted in significant reduction in inflammatory response (reduced γ-IFN and granzyme expression) in recipient mice as compared to the control group. Microarray analysis revealed a significant up-regulation of IL-27 gene (30 fold) in kidney resident DNT cells in comparison to CD4 and CD8 cells isolated from kidneys and a significant up-regulation in IL-10 gene (16 fold) after IRI in sorted DN T cells compared to baseline.
Conclusions Our data shows that kidney resident DN T cells are innate-like cells and a primary responder to ischemia reperfusion injury. Understanding the role of DNT in the kidney could have important therapeutic implications for IRI as well as alloresponses in transplantation.
To cite this abstract in AMA style:
Martina M, Bandapalle S, Noel S, Saxena A, Hamad A, Rabb H. Kidney Double Negative TCR αβ + Cells: Newly Described Intra-Renal Kidney Lymphocytes That Respond to Ischemia Reperfusion in Mice [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/kidney-double-negative-tcr-cells-newly-described-intra-renal-kidney-lymphocytes-that-respond-to-ischemia-reperfusion-in-mice/. Accessed May 19, 2025.« Back to 2015 American Transplant Congress