Activated (IL-2R+) intraglomerular mononuclear cells in crescentic glomerulonephritis. We recently reported evidence for the involvement of local cellular immune activation in the immunopathogenesis of human IgA nephropathy, particularly in cases of IgA disease featuring crescent formation. In the current study, using monoclonal antibodies, we investigated whether mononuclear cells bearing receptors for inter-leukin 2 (IL-2R+ MNC) were present within glomeruli or associated crescents in biopsies from patients with crescentic glomerulonephritis (> 60% crescents, N = 19), IgA disease with crescents (N = 9), or other types of proliferative glomerulonephritis with crescents (10 to 44%, N = 6), compared with normal control kidneys (N = 10). Biopsies were further classified into those showing active (cells, fibrin) (N = 15) or inactive (sclerosed) crescents (N = 19), to determine whether IL-2R+ MNC were particularly associated with active crescent formation. Few leucocytes were found within glomerular tufts of normal kidneys (2.4 ± 0.7 cells/glomerular cross-section; mean ± SEM). By contrast, in biopsies from patients with active crescentic glomerulonephritis, total intraglomerular tuft leucocytes were increased to 14.0 ± 1.7 (P < 0.01 vs. normal kidneys), largely due to increased numbers of intraglomerular monocytes (10.4 ± 1.1, P < 0.01) and T cells (3.7 ± 0.6, P < 0.01). Biopsies with active crescents also contained significantly increased numbers of intraglomerular tuft IL-2R+ MNC (4.0 ± 0.7, 29% of total intraglomerular leucocytes), and there was a strong correlation between the numbers of intraglomerular IL-2R+ MNC and T cells (P < 0.001). Moreover, in this active crescentic group, increases in the numbers of intraglomerular IL-2R+ MNC (P < 0.05), macrophages (P < 0.01) and T cells (P < 0.01) were correlated with raised serum creatinine levels, and the numbers of both IL-2R+ MNC (P < 0.05) and macrophages (P < 0.01) correlated with decreased creatinine clearance. Patients with inactive crescentic glomerulonephritis also showed increased levels of tuft MNC compared to normal kidneys, but significantly less intraglomerular MNC than biopsies from patients with active crescentic disease. Thus, in inactive crescentic disease there was a four-fold increase in glomerular MNC infiltration (total leucocytes 10.0 ± 1.4, P < 0.01), due to macrophages (6.6 ± 1.0, P < 0.01 compared to normals or active crescentic glomerulonephritis) and T cells (2.9 ± 0.3, P < 0.01), and including IL-2R+ MNC (2.2 ± 0.3, P < 0.01 compared to normals or active crescentic disease). The cellular composition of actual crescents was also determined. Leucocytes contributed more than 60% of the total cells within active crescents, due primarily to the presence of macrophages (43.1% ± 5.1%) and T cells (7.1% ± 2.1%); 8% of these leucocytes within crescents were IL-2R+. Glomeruli with active crescents contained extensive ruptures of Bowman's capsules. Inactive crescents, which generally displayed intact Bowman's capsules, pre-sumeably as a result of fresh synthesis of basement membrane components, contained fewer leucocytes (19.1% ± 2.2%), including reduced numbers of macrophages (7.2% ± 1.9%) and T cells (0 to 3, ranges). Given the close regulation of IL-2R expression on activated MNC, and the correlations observed between the presence of activated intraglomerular tuft MNC and decreased parameters of renal function, these results suggest that crescent formation involves recruitment of macrophages to the glomerulus by sensitised T cells, analogous to events occurring in a DTH response, and are consistent with a direct role for cellular immunity in the …