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Activated (IL-2R+) intraglomerular mononuclear cells in crescentic glomerulonephritis
H L Li1, W W Hancock, J P Dowling
1Department of Nephrology, Prince Henry's Hospital, Melbourne, Victoria, Australia.
Insights
Immune cells, specifically interleukin-2 receptor-bearing mononuclear cells (IL-2R+ MNC), are significantly increased in active crescentic glomerulonephritis, correlating with T cell numbers.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Local cellular immune activation is implicated in IgA nephropathy pathogenesis, especially with crescent formation.
- The role of specific immune cells in crescentic glomerulonephritis requires further elucidation.
Purpose of the Study:
- To investigate the presence and significance of interleukin-2 receptor-positive mononuclear cells (IL-2R+ MNC) in kidney biopsies from patients with various forms of glomerulonephritis and crescents.
- To determine if IL-2R+ MNC are associated with active crescent formation.
Main Methods:
- Monoclonal antibodies were used to identify IL-2R+ MNC in kidney biopsies.
- Biopsies included crescentic glomerulonephritis, IgA disease with crescents, other proliferative glomerulonephritis with crescents, and normal controls.
- Samples were classified based on the presence of active (cellular, fibrin) or inactive (sclerosed) crescents.
Main Results:
- Active crescentic glomerulonephritis biopsies showed significantly increased total intraglomerular leukocytes, monocytes, and T cells compared to normal kidneys.
- Increased numbers of intraglomerular IL-2R+ MNC were found in biopsies with active crescents.
- A strong correlation was observed between intraglomerular IL-2R+ MNC and T cell counts.
Conclusions:
- IL-2R+ MNC are significantly elevated in active crescentic glomerulonephritis.
- The presence of IL-2R+ MNC is closely linked to T cell infiltration and active crescent formation in the glomeruli.
- These findings highlight the role of activated T cells in the immunopathogenesis of crescentic glomerulonephritis.
Abstract:
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 interleukin 2 (IL-2R+ MNC) were present within glomeruli or associated crescents in biopsies from patients with crescentic glomerulonephritis (greater than 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 less than 0.01 vs. normal kidneys), largely due to increased numbers of intraglomerular monocytes (10.4 +/- 1.1, P less than 0.01) and T cells (3.7 +/- 0.6, P less than 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 less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
