T cells direct macrophage recruitment and giant cell formation but not proliferation in experimental crescentic glomerulonephritis.

Abstract

The role of T cells in directing macrophage recruitment and proliferation and giant cell formation was studied in crescentic glomerulonephritis (GN) in rats. Development of GN was associated with a significant glomerular influx of T cells and macrophages and crescent formation. Multi-nucleated giant cells (MGCs) were also prominent in glomeruli and most frequently associated with crescents. Their phenotype suggested that they were derived from recently recruited blood monocytes. The majority of glomerular macrophages and MGCs showed evidence of recent proliferation. T cell depletion using anti-CD5 or anti-CD4 monoclonal antibodies significantly reduced T cells and macrophage accumulation, crescent formation (anti-CD5 treated 12 +/- 4.0%; anti-CD4 treated 13 +/- 3.0%; control 64 +/- 10%; P<0.001) and MGC formation [anti-CD5 treated 0.06 +/- 0.01 cells per glomerular cross section (c/gcs); anti-CD4 treated 0.06 +/- 0.01 c/gcs; control treated 1.2 +/- 0.1 c/gcs; P<0.001]. The proliferation index (fraction of cells expressing proliferating cell nuclear antigen) of macrophages and MGCs was not affected by T cell depletion (macrophage proliferation index: anti-CD5 treated 0.88 +/- 0.04; anti-CD4 treated 0.83 +/- 0.02; control 0.85 +/- 0.02; MGC proliferation index: anti-CD5 treated 0.84 +/- 0.06; anti-CD4 treated 0.86 +/- 0.04; control 0.90 +/- 0.05). These studies demonstrate that glomerular macrophage recruitment, MGC and crescent formation are dependent on T helper cells but proliferation of macrophages and MGCs is independent of T cells. This suggests that the major mechanism for T cell induced macrophage accumulation in crescentic GN is via directing their recruitment rather than their local proliferation. Giant cell formation, which is also predominantly T cell dependent, appears to be independent of their proliferative activity.