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The Journal of Immunology, 2006, 177: 3380-3387.
Copyright © 2006 by The American Association of Immunologists, Inc.

Phenotypic and Functional Characterization of Kidney-Infiltrating Lymphocytes in Renal Ischemia Reperfusion Injury1

Dolores B. Ascon*, Sergio Lopez-Briones*, Manchang Liu*, Miguel Ascon*, Vladimir Savransky*, Robert B. Colvin{dagger}, Mark J. Soloski* and Hamid Rabb2,*

* Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and {dagger} Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115

T and B lymphocytes have been implicated in the pathogenesis of renal ischemia reperfusion injury (IRI). The trafficking of lymphocytes into kidneys during IRI has been postulated to underlie this effect, but has not been rigorously studied. We therefore characterized the lymphocyte populations infiltrating into mouse kidneys 3 and 24 h after renal IRI. Immunohistochemistry and flow cytometry staining of kidney lymphocytes showed increased trafficking of CD3+ T cells and CD19+ B cells in both sham-operated and IRI mice 3 h after renal IRI. In the IRI mice, increased infiltration of NK1.1+ and CD4+NK1.1+ cells compared with normal and sham-operated mice was observed 3 and 24 h after renal IRI, respectively. After 24 h of renal IRI, the decreased percentages of CD3+, CD19+, and NK1.1+ populations in the IRI mice compared with control groups were observed. Increased TNF-{alpha} and IFN-{gamma} production of kidney infiltration CD3+ T cells in IRI mice but not sham-operated mice was found. Unexpectedly, isolation and transfer of kidney-infiltrating lymphocytes 24 h after renal IRI into T cell-deficient mice reduced their functional and histological injury after renal IRI, suggesting that kidney-infiltrating lymphocytes could have a protective function. These quantitative, qualitative, and functional changes in kidney lymphocytes provide mechanistic insight into how lymphocytes modulate IRI, as well as demonstrating that abdominal surgery alone leads to lymphocyte changes in kidney.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This study was supported by grants from the National Institutes of Health minority supplement for the R0–1 DK54770 and a Roche Organ Transplantation Research Foundation award.

2 Address correspondence and reprint requests to Dr. Hamid Rabb, Johns Hopkins University School of Medicine, Ross Research Building, Room 970, 720 Rutland Avenue, Baltimore, MD 21205. E-mail address: hrabb1{at}jhmi.edu

3 Abbreviations used in this paper: IRI, ischemia reperfusion injury; KMNC, kidney mononuclear cell; HPF, high-power field.




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