T cells reactive to an inducible heat shock protein induce disease in toxin-induced interstitial nephritis.

T cells reactive against immunodominant regions of inducible heat shock proteins (HSPs) have been identified in the chronic inflammatory lesions of several experimental autoimmune diseases. Since HSPs are known to be induced by a number of renal tubular epithelial cell toxins associated with chronic interstitial nephritis, we investigated the relevance of HSP expression and T cell reactivity to HSP70 in a model of progressive inflammatory interstitial nephritis. Chronic administration of cadmium chloride (CdCl2) to SJL/J mice induces HSP70 expression in renal tubular cells 4-5 wk before the development of interstitial mononuclear cell infiltrates. CdCl2 also induces HSP70 expression in cultured tubular epithelial cells from SJL/J mice. CD4+, TCR-alpha/beta+ T cell lines specific for an immunodominant HSP peptide are cytotoxic to heat stressed or CdCl2-treated renal tubular cells. Such HSP-reactive T cells mediate an inflammatory interstitial nephritis after adoptive transfer to CdCl2-treated mice at a time when immunoreactive HSP70 is detectable in the kidneys, but before the development of interstitial mononuclear cell infiltrates. T cells isolated from the nephritic kidneys of mice treated with CdCl2 for 13 wk are also cytotoxic to heat shocked or cadmium-treated tubular cells. These kidney-derived T cells additionally induced interstitial nephritis after passive transfer, indicating their pathogenic significance. Our studies strongly support a role for HSP-reactive T cells in CdCl2-induced interstitial nephritis and suggest that the induction of HSPs in the kidney by a multitude of "non-immune" events may initiate or facilitate inflammatory damage by HSP-reactive lymphocytes.

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Small Heat Shock Protein Beta-1 (HSPB1) Is Upregulated and Regulates Autophagy and Apoptosis of Renal Tubular Cells in Acute Kidney Injury

PLoS ONE ◽

10.1371/journal.pone.0126229 ◽

2015 ◽

Vol 10 (5) ◽

pp. e0126229 ◽

Cited By ~ 32

Author(s):

Tatsuki Matsumoto ◽

Madoka Urushido ◽

Haruna Ide ◽

Masayuki Ishihara ◽

Kazu Hamada-Ode ◽

...

Keyword(s):

Acute Kidney Injury ◽

Heat Shock ◽

Heat Shock Protein ◽

Kidney Injury ◽

Small Heat Shock Protein ◽

Tubular Cells ◽

Renal Tubular Cells ◽

Renal Tubular

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EFFECTS OF NUCLEAR FACTOR OF ACTIVATED T-CELLS 5 (NFAT5) KNOCKOUT IN RENAL TUBULAR CELLS ON RENAL FIBROGENESISNFAT5 (NUCLEAR FACTOR OF ACTIVATED T-CELLS 5) IS A TRANSCRIPTION FACTOR

Journal of Hypertension ◽

10.1097/01.hjh.0000747928.32857.35 ◽

2021 ◽

Vol 39 (Supplement 1) ◽

pp. e300-e301

Author(s):

Yuichiro Izumi ◽

Makoto Ono ◽

Koji Eguchi ◽

Naomi Matsuo ◽

Akiko Hiramatsu ◽

...

Keyword(s):

T Cells ◽

Transcription Factor ◽

Nuclear Factor ◽

Activated T Cells ◽

Tubular Cells ◽

Renal Tubular Cells ◽

Renal Tubular

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Heat shock prevents simulated ischemia-induced apoptosis in renal tubular cells via a PKC-dependent mechanism

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2001.281.1.r359 ◽

2001 ◽

Vol 281 (1) ◽

pp. R359-R364 ◽

Cited By ~ 27

Author(s):

K. K. Meldrum ◽

D. R. Meldrum ◽

S. F. Sezen ◽

J. K. Crone ◽

A. L. Burnett

Keyword(s):

Heat Stress ◽

Thermal Stress ◽

Heat Shock ◽

Ischemic Tolerance ◽

Tubular Cells ◽

Renal Tubular Cells ◽

Simulated Ischemia ◽

Renal Tubular ◽

Induced Apoptosis ◽

Dependent Mechanism

Heat shock produces cellular tolerance to a variety of adverse conditions; however, the protective effect of heat shock on renal cell ischemic injury remains unclear. Protein kinase C (PKC) has been implicated in the signaling mechanisms of acute preconditioning, yet it remains unknown whether PKC mediates heat shock-induced delayed preconditioning in renal cells. To study this, renal tubular cells (LLC-PK1) were exposed to thermal stress (43°C) for 1 h and heat shock protein (HSP) 72 induction was confirmed by Western blot analysis. Cells were subjected to simulated ischemia 24 h after thermal stress, and the effect of heat shock (delayed preconditioning) on ischemia-induced apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling) and B cell lymphoma 2 (Bcl2) expression (Western) was determined. Subsequently, the effect of PKC inhibition on HSP72 induction and heat stress-induced ischemic tolerance was evaluated. Thermal stress induced HSP72 production, increased Bcl2 expression, and prevented simulated ischemia-induced renal tubular cell apoptosis. PKC inhibition abolished thermal induction of HSP72 and prevented heat stress-induced ischemic tolerance. These data demonstrate that thermal stress protects renal tubular cells from simulated ischemia-induced apoptosis through a PKC-dependent mechanism.

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Angiocentric CD3+ T-Cell Infiltrates in Human Immunodeficiency Virus Type 1-Associated Central Nervous System Disease in Children

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.6.1.105-114.1999 ◽

1999 ◽

Vol 6 (1) ◽

pp. 105-114 ◽

Cited By ~ 24

Author(s):

Christos D. Katsetos ◽

John E. Fincke ◽

Agustin Legido ◽

Harold W. Lischner ◽

Jean-Pierre de Chadarevian ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

T Cell ◽

Brain Tissue ◽

Mononuclear Cell ◽

Immunodeficiency Virus ◽

Tissue Specimens ◽

Mononuclear Cell Infiltrates ◽

Hiv 1

ABSTRACT A significant proportion of brain tissue specimens from children with AIDS show evidence of vascular inflammation in the form of transmural and/or perivascular mononuclear-cell infiltrates at autopsy. Previous studies have shown that in contrast to inflammatory lesions observed in human immunodeficiency virus type 1 (HIV-1) encephalitis, in which monocytes/macrophages are the prevailing mononuclear cells, these infiltrates consist mostly of lymphocytes. Perivascular mononuclear-cell infiltrates were found in brain tissue specimens collected at autopsy from five of six children with AIDS and consisted of CD3+ T cells and equal or greater proportions of CD68+ monocytes/macrophages. Transmural (including endothelial) mononuclear-cell infiltrates were evident in one patient and comprised predominantly CD3+ T cells and small or, in certain vessels, approximately equal proportions of CD68+monocytes/macrophages. There was a clear preponderance of CD3+ CD8+ T cells on the endothelial side of transmural infiltrates. In active lesions of transmural vasculitis, CD3+ T-cell infiltrates exhibited a distinctive zonal distribution. The majority of CD3+ cells were also CD8+ and CD45RO+. Scattered perivascular monocytes/macrophages in foci of florid vasculitis were immunoreactive for the p24 core protein. In contrast to the perivascular space, the intervening brain neuropil was dominated by monocytes/macrophages, microglia, and reactive astrocytes, containing only scant CD3+ CD8+ cells. Five of six patients showed evidence of calcific vasculopathy, but only two exhibited HIV-1 encephalitis. One patient had multiple subacute cerebral and brainstem infarcts associated with a widespread, fulminant mononuclear-cell vasculitis. A second patient had an old brain infarct associated with fibrointimal thickening of large leptomeningeal vessels. These infiltrating CD3+ T cells may be responsible for HIV-1-associated CNS vasculitis and vasculopathy and for endothelial-cell injury and the opening of the blood-brain barrier in children with AIDS.

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