Role of T lymphocytes in renal disease in HIV-transgenic mice.
The pathogenesis of human immunodeficiency virus (HIV)-associated focal segmental 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 thus could be targets for cytotoxic T lymphocytes. We previously described mice transgenic for a gag-pol-deleted HIV-1 genome that developed FSGS. In the present study, we tested the requirement for functional T cells in the evolution of renal disease in this model. We bred the HIV-transgenic mice (T26) with athymic nude mice to produce athymic T26 mice. We confirmed by flow cytometry of peripheral blood, thymus, lymph node, and spleen that the athymic T26 mice lacked mature T cells. The athymic T26 mice developed renal disease characterized by FSGS, tubular atrophy and dilatation, and interstitial infiltrate that was qualitatively identical to that seen in the parental T26 mice. Quantitative assessment of the athymic T26 mouse kidneys showed that glomerulosclerosis, tubular injury, and interstitial infiltrate were less severe compared with the parental T26 mouse kidneys. Although T26 mouse kidneys had a mixed cellular infiltrate composed of CD4 cells, CD8 cells, and macrophages, interstitial infiltrates within the athymic T26 mouse kidneys included macrophages but lacked both CD4 and CD8 cells. The renal expression 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 required for the development of HIV-associated nephropathy in transgenic mice but that, in their absence, renal disease is significantly milder. These data suggest that T-cell-mediated cytotoxicity directed against renal cells expressing virally encoded proteins is not an essential feature of renal pathogenesis in this model.
Shrivastav
S
S
Kidney Disease Section, Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, and Oral Infection and Immunity Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD, USA.
Cusumano
A
A
Kanno
Y
Y
Chen
G
G
Bryant
J L
JL
Kopp
J B
JB
D000818:Animals; D030801:Animals, Genetically Modified; D018791:CD4 Lymphocyte Count; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000503:physiopathology / Q000821:virology*; D015658:HIV Infections / Q000150:complications*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D013601:T-Lymphocytes / Q000502:physiology*