Interstitial Activated (Il-2R+) Mononuclear Cells And La Antigens In Experimental Focal Glomerulosclerosis*

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Tubulointerstitial localization of major histocompatibility complex (MHC) class II (la) antigens and immune-activated mononuclear cells (IL-2R+) and its suppression by prednisolone (PSL) were studied in a progressive model of focal glomerulosclerosis (FGS) induced by aminonucleoside (AN) and protamine sulfate (PS) given as 4 four day courses in rats. Tissues were prepared for the quantification of leucocytes on days 24, 52 and 80. The numbers of total leucocytes (CD45+), la+ cells, monocytes/macrophages, T lymphocytes (CD5+) and IL-2R+ cells (CD25+) were enumerated in immunoperoxidase sections using monoclonal antibodies: OX1, OX6, ED1, OX19 and ART18, respectively. The effects of PSL at a dose of 3 mg/kg body weight, which was begun from day 30, 12 days after the second series of injections, and continued for 50 days, were studied on day 80. There was no significant increase of glomerular T cells or IL-2R+ cells throughout the study. By contrast, each cell group in the interstitium increased in number throughout the disease evolution. Specifically IL-2R+ cells, which were rarely seen before AN + PS injection, were expressed by 5% of total leucocytes on day 80. la antigens also increased time-dependently and were found in proximal tubular cells on day 80. PSL treatment suppressed IL-2R and la expression in proportion to the decrease of total leucocytes and T cells.

These results imply that delayed type hypersensitivity related to the appearance of immune activated T cells (IL-2R+) and MHC class II antigens may play a role in the progression of interstitial lesions and consequent renal dysfunction in a nonimmune-initiated FGS model.

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