CD4+CD25+ regulatory T cells attenuate cisplatin-induced nephrotoxicity in mice.

Abstract

Nephrotoxicity limits the use of cisplatin, a widely used chemotherapeutic agent for treatment of various malignancies. Overall, CD4+ T cells mediate cisplatin-induced renal injury; however, the CD4+CD25+ regulatory T-cell subset (CD4+CD25+ Treg) has broad suppressive effects on many different cell types. In this study, we determined whether CD4+CD25+ Treg cells had protective effects against cisplatin-induced acute renal injury in nu/nu mice that lack mature T cells. In these mice, there was marked attenuation of the decreased survival, renal dysfunction and tubular injury, renal tumor necrosis factor-α, and interleukin-1β cytokine levels. Furthermore, renal macrophage accumulation was reduced in CD4+CD25+ Treg cell-adoptive transferred nu/nu mice compared with control mice. Infusion of CD4+CD25+Treg cells into wild-type Balb/c mice reduced serum blood urea nitrogen and creatinine levels equivalent to those in nu/nu mice and extended their survival time after cisplatin injection. In contrast, depletion of CD4+CD25+ Treg cells in wild-type mice exacerbated kidney injury after cisplatin administration. Transcription factor Foxp3-positive cells (Treg cells) were detected in the kidneys of nu/nu mice after cisplatin injection. Our results suggest that CD4+CD25+ Treg cells directly affect cisplatin nephrotoxicity and their modulation represents an additional treatment strategy.

• Authors: Hyojung Lee, Dukhee Nho, Hwan-Suck Chung, Heekyung Lee, Min-Kyu Shin, Sung-Hoon Kim, Hyunsu Bae
• Journal: Kidney international (Kidney Int) Vol. 78 Issue 11 Pg. 1100-9 (Dec 2010) ISSN: 1523-1755 [Electronic] United States
• PMID: 20463654 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Forkhead Transcription Factors
• Foxp3 protein, mouse
• IL2RA protein, human
• Inflammation Mediators
• Interleukin-1beta
• Interleukin-2 Receptor alpha Subunit
• Tumor Necrosis Factor-alpha
• Creatinine
• Cisplatin

Topics

• Adoptive Transfer
• Animals
• Biomarkers (blood)
• Blood Urea Nitrogen
• Chemotaxis, Leukocyte
• Cisplatin
• Creatinine (blood)
• Disease Models, Animal
• Forkhead Transcription Factors (metabolism)
• Immunity, Innate
• Inflammation Mediators (metabolism)
• Interleukin-1beta (metabolism)
• Interleukin-2 Receptor alpha Subunit (analysis)
• Kidney (immunology, metabolism, pathology)
• Kidney Diseases (blood, chemically induced, immunology, pathology, prevention & control)
• Macrophages (immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• T-Lymphocyte Subsets (immunology, transplantation)
• T-Lymphocytes, Regulatory (immunology, transplantation)
• Time Factors
• Tumor Necrosis Factor-alpha (metabolism)