I L-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 (α, β, γ 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.