IMMUNE EVENTS IN LYMPHOID-TISSUES DURING EXPERIMENTAL GLOMERULONEPHRITIS

To investigate immune events within lymphoid tissues and their role in relation to glomerular disease, systemic lymphoid tissues from rats w ith accelerated experimental anti-GBM glomerulonephritis or with prime d serum sickness glomerulopathy were studied. Following disease induct ion, changes in leukocytic populations within lymphoid tissues were an alysed over a 28 day time course by immunoperoxidase labelling with mo noclonal antibodies. In anti-GBM glomerulonephritis there was rapid an d severe renal injury and pulmonary hemorrhage (Good-pasture's syndrom e). In these rats, antigen (rabbit IgG) was deposited on the GBM and w ithin germinal centres of lymphoid tissues. From day 3 onwards, there was a significant increase in the number of T cells, presumably CD4+ T helper cells, present within enlarged germinal centres of kidney drai ning lymph nodes, axillary lymph nodes and spleen (p < 0.05) which pea ked at day 14 (up to 28% of total cells) when there was intense deposi tion of rat IgG and C3 on the GBM. Similarly, increased numbers of ED1 + macrophages were evident in both germinal centres and T cell areas ( paracortex and periarteriolar lymphoid sheath). Notably, the appearanc e of IL-2R expression in germinal centres and T cell areas was apparen t from day 7 onwards. This was the time when widespread renal intersti tial infiltration, cellular immune activation and severe renal functio nal and histological injury developed. In addition, antigen deposited in germinal centres was found to be associated with CD4+, CD5-, ED1- c ells, most probably antigen presenting dendritic cells. In contrast, i n acute serum sickness there was no antigen deposited in germinal cent res and only mild renal injury and minor changes within lymphoid tissu es. These results suggest that immune activation within systemic lymph oid tissues may amplify the immunological injury within the kidney and thus exacerbate the progression of glomerulonephritis.