IL-15, a T cell growth factor, has been linked to exacerbating autoimmune diseases and allograft rejection.To test the hypothesis that IL-15-deficient (IL-15 -/-) mice would be protected from T cell-dependent nephritis, we induced nephrotoxic serum nephritis (NSN) in IL-15 -/-and wild-type (IL-15 +/+ ) C57BL/6 mice.Contrary to our expectations, IL-15 protects the kidney during this T cell-dependent immunologic insult.Tubular, interstitial, and glomerular pathology and renal function are worse in IL-15 -/-mice during NSN.We detected a substantial increase in tubular apoptosis in IL-15 -/-kidneys.Moreover, macrophages and CD4 T cells are more abundant in the interstitia and glomeruli in IL-15 -/-mice.This led us to identify several mechanisms responsible for heightened renal injury in the absence of IL-15.We now report that IL-15 and the IL-15 receptor (, , chains) are constitutively expressed in normal tubular epithelial cells (TECs).IL-15 is an autocrine survival factor for TECs.TEC apoptosis induced with anti-Fas or actinomycin D is substantially greater in IL-15 -/-than in wild-type TECs.Moreover, IL-15 decreases the induction of a nephritogenic chemokine, MCP-1, that attracts leukocytes into the kidney during NSN.Taken together, we suggest that IL-15 is a therapeutic for tubulointerstitial and glomerular kidney diseases.
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Shinozaki et al. (2002) studied this question.
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