Abstract
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 (CdClz) to SJL/J mice induces HSP70 expression in renal tubular cells 4-5 wk before the development of interstitial mononuclear cell infiltrates. CdC12 also induces HSP70 expression in cultured tubular epithelial cells from SJL/J mice. CD4+, TCR-α/β+T cell lines specific for an immunodominant HSP peptide are cytotoxic to heat stressed or CdClz-treated renal tubular cells. Such HSP-reactive T cells mediate an inflammatory interstitial nephritis after adoptive transfer to CdClz-treated mice at a time when immunoreactive HSPT0 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 CdC12 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 ceils in CdC12-induced interstitial nephritis and suggest that the induction of HSPs in the kidney by a multitude of "nonimmune" events may initiate or facilitate inflammatory damage by HSP-reactive lymphocytes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2239-2250 |
| Number of pages | 12 |
| Journal | Journal of Experimental Medicine |
| Volume | 180 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 1 1994 |
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ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
T cells reactive to an inducible heat shock protein induce disease in toxin-induced interstitial nephritis. / Weiss, Roberta A.; Madaio, Michael P.; Tomaszewski, John E.; Kelly, Carolyn J.
In: Journal of Experimental Medicine, Vol. 180, No. 6, 01.12.1994, p. 2239-2250.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - T cells reactive to an inducible heat shock protein induce disease in toxin-induced interstitial nephritis
AU - Weiss, Roberta A.
AU - Madaio, Michael P.
AU - Tomaszewski, John E.
AU - Kelly, Carolyn J.
PY - 1994/12/1
Y1 - 1994/12/1
N2 - 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 (CdClz) to SJL/J mice induces HSP70 expression in renal tubular cells 4-5 wk before the development of interstitial mononuclear cell infiltrates. CdC12 also induces HSP70 expression in cultured tubular epithelial cells from SJL/J mice. CD4+, TCR-α/β+T cell lines specific for an immunodominant HSP peptide are cytotoxic to heat stressed or CdClz-treated renal tubular cells. Such HSP-reactive T cells mediate an inflammatory interstitial nephritis after adoptive transfer to CdClz-treated mice at a time when immunoreactive HSPT0 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 CdC12 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 ceils in CdC12-induced interstitial nephritis and suggest that the induction of HSPs in the kidney by a multitude of "nonimmune" events may initiate or facilitate inflammatory damage by HSP-reactive lymphocytes.
AB - 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 (CdClz) to SJL/J mice induces HSP70 expression in renal tubular cells 4-5 wk before the development of interstitial mononuclear cell infiltrates. CdC12 also induces HSP70 expression in cultured tubular epithelial cells from SJL/J mice. CD4+, TCR-α/β+T cell lines specific for an immunodominant HSP peptide are cytotoxic to heat stressed or CdClz-treated renal tubular cells. Such HSP-reactive T cells mediate an inflammatory interstitial nephritis after adoptive transfer to CdClz-treated mice at a time when immunoreactive HSPT0 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 CdC12 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 ceils in CdC12-induced interstitial nephritis and suggest that the induction of HSPs in the kidney by a multitude of "nonimmune" events may initiate or facilitate inflammatory damage by HSP-reactive lymphocytes.
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U2 - 10.1084/jem.180.6.2239
DO - 10.1084/jem.180.6.2239
M3 - Article
VL - 180
SP - 2239
EP - 2250
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 6
ER -