Role of T lymphocytes in renal disease in HIV-transgenic mice

The pathogenesis of human immunodeficiency virus (HIV) associated focal seg mental glomerulosclerosis (FSGS) has remained obscure. It has been proposed that renal parenchymal cells may be infected with HIV-1, If such infection occurs, the target cells would be expected to express viral proteins and t hus could be targets for cytotoxic T lymphocytes. We previously described m ice transgenic for a gag-pol-deleted HIV-1 genome that developed FSGS. In t he present study, we tested the requirement for functional T cells in the e volution of renal disease in this model, We bred the HIV-transgenic mice (T 26) with athymic nude mice to produce athymic T26 mice. We confirmed by flo w cytometry of peripheral blood, thymus, lymph node, and spleen that the at hymic T26 mice lacked mature T cells. The athymic T26 mice developed renal disease characterized by FSGS, tubular atrophy and dilatation, and intersti tial infiltrate that was qualitatively identical to that seen in the parent al T26 mice. Quantitative assessment of the athymic T26 mouse kidneys showe d that glomerulosclerosis, tubular injury, and interstitial infiltrate were less severe compared with the parental T26 mouse kidneys, Although T26 mou se kidneys had a mixed cellular infiltrate composed of CD4 cells, CD8 cells , and macrophages, interstitial infiltrates within the athymic T26 mouse ki dneys included macrophages but lacked both CD4 and CD8 cells. The renal exp ression of the HIV transgene was 1.7-fold greater in T26 mice compared with athymic T26 mice. We conclude that mature T cells are not absolutely requi red for the development of HIV-associated nephropathy in transgenic mice bu t that, in their absence, renal disease is significantly milder. These data suggest that T-cell-mediated cytotoxicity directed against renal cells exp ressing virally encoded proteins is not an essential feature of renal patho genesis in this model. (C) 2000 by the National Kidney Foundation, Inc.