Abstract | BACKGROUND: CD4(+) T cells play an important role in various types of immunologic renal disease, including lupus nephritis, IgA nephropathy, and crescentic glomerulonephritis. CD4(+) T cells are also major infiltrating lymphocytes in chronic tubulointerstitial inflammation associated with nonimmunological renal diseases. We suspected that CD4(+) T cells might contribute to disease progression and loss of renal function in chronic proteinuric renal disease (CPRD). To investigate this possibility, the effect of monoclonal antibody against CD4(+) lymphocytes (anti-CD4) was studied in a murine model ( adriamycin nephropathy) of CPRD. METHODS: RESULTS: Flow cytometric analysis showed a marked decrease in the number of CD4(+) T cells in blood and spleen of the antibody-treated animals (N = 7, P < 0.01). Adriamycin plus CD4(+) depletion mice had significantly greater mesangial expansion, glomerular sclerosis, and interstitial expansion than the mice on adriamycin alone. Interstitial infiltration with macrophages and CD8(+) cells was significantly increased in adriamycin plus CD4(+) depletion mice. Creatinine clearance (17.5 +/- 0.54 vs. 29.2 +/- 0.89 microL/min, P < 0.001) was significantly worse in the adriamycin plus CD4(+) depletion mice than in adriamycin alone mice and correlated with histologic change in glomeruli and interstitium. CONCLUSIONS: Depletion of CD4(+) T cells promotes glomerular and interstitial injury in mice with established adriamycin nephropathy. These findings suggest that CD4(+) T cells have a protective role against the progression of adriamycin nephropathy.
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Authors | Y Wang, Y Wang, X Feng, S Bao, S Yi, L Kairaitis, Y C Tay, G K Rangan, D C Harris |
Journal | Kidney international
(Kidney Int)
Vol. 59
Issue 3
Pg. 975-84
(Mar 2001)
ISSN: 0085-2538 [Print] United States |
PMID | 11231352
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Monoclonal
- RNA, Messenger
- Interleukin-4
- Doxorubicin
- Interferon-gamma
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Topics |
- Animals
- Antibodies, Monoclonal
(pharmacology)
- CD4 Lymphocyte Count
- CD4-Positive T-Lymphocytes
(immunology, pathology, physiology)
- Doxorubicin
- Interferon-gamma
(genetics)
- Interleukin-4
(genetics)
- Kidney
(metabolism, pathology)
- Kidney Diseases
(chemically induced, metabolism, pathology)
- Kidney Glomerulus
(metabolism, pathology)
- Macrophages
(pathology)
- Male
- Mice
- Mice, Inbred BALB C
- Monocytes
(pathology)
- RNA, Messenger
(metabolism)
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