Glomerular proliferative activity and T lymphocyte infiltration in acute serum sickness

Because hypercellularity is an important feature in acute serum sickness (AcSS), we quantified glomerular proliferation with immunoperoxidase staining using anti-proliferating cell nuclear antigen (PCNA Mab) and studied its relationship with lymphocyte infiltration (M108 Mab). AcSS was induced in 31 New Zealand White rabbits; group A (n = 14), with proteinuria, sacrificed 6-8 days after immunization; group B (n = 10), without proteinuria, sacrificed 6-7 days after immunization; group C (n = 7), sacrificed prior to development of AcSS. Four normal rabbits were included as controls. Intraglomerular proliferation (PCNA-positive cells/glomerular cross section) was increased in group A (12.2 +/- SEM, 1.84) but not in groups B (0.93 +/- 0.17) and C (0.37 +/- 0.05), which were similar to controls (0.66 +/- 0.06). Lymphocyte infiltration (lymphs/glomerular cross section) increased with time and was more prominent in rabbits with proteinuria (1.9 +/- 0.21, P < 0.001 vs controls). Lymphocyte infiltration was correlated with proliferative activity (Spearman correlation, r = 0.67, P < 0.0001). There was correlation between the severity of glomerular deposition of IgG and C3 and glomerular proliferation and proteinuria. These studies demonstrate a chronological association between lymphocyte infiltration and proliferative activity in AcSS.