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 with accelerated experimental anti-GBM glomerulonephritis or with primed serum sickness glomerulopathy were studied. Following disease induction, changes in leukocytic populations within lymphoid tissues were analysed over a 28 day time course by immunoperoxidase labelling with monoclonal antibodies. In anti-GBM glomerulonephritis there was rapid and severe renal injury and pulmonary hemorrhage (Good-pasture's syndrome). In these rats, antigen (rabbit IgG) was deposited on the GBM and within 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 draining lymph nodes, axillary lymph nodes and spleen (p < 0.05) which peaked at day 14 (up to 28% of total cells) when there was intense deposition 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 appearance of IL-2R expression in germinal centres and T cell areas was apparent from day 7 onwards. This was the time when widespread renal interstitial infiltration, cellular immune activation and severe renal functional and histological injury developed. In addition, antigen deposited in germinal centres was found to be associated with CD4+, CD5-, ED1- cells, most probably antigen presenting dendritic cells. In contrast, in acute serum sickness there was no antigen deposited in germinal centres and only mild renal injury and minor changes within lymphoid tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
Lan
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Department of Nephrology, Monash Medical Centre, Clayton, Victoria, Australia.
Nikolic-Paterson
D J
DJ
Atkins
R C
RC
D000208:Acute Disease; D000818:Animals; D005921:Glomerulonephritis / Q000276:immunology* / Q000473:pathology; D007074:Immunoglobulin G / Q000032:analysis; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015375:Receptors, Interleukin-2 / Q000032:analysis; D012713:Serum Sickness / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets
D007074:Immunoglobulin G; D015375:Receptors, Interleukin-2