CRESCENTIC GLOMERULONEPHRITIS IN CD4-DEFICIENT AND CD8-DEFICIENT MICE- REQUIREMENT FOR CD4 BUT NOT CD8 CELLS

The contribution of CD4 and CD8 cells to crescentic glomerulonephritis (GN) was studied in mice genetically deficient in CD4, CD8, and with combined CD4 and CD8 (CD4/CD8) deficiency. Wild-type (C57BL/6) mice de veloped GN with mild proliferative changes 7 days after an intravenous dose of sheep anti-mouse glomerular basement membrane globulin. Cresc ents were observed in 12.5 +/- 6.1% of glomeruli on day 14, On day 21, 51.5 +/- 7.3% of glomeruli were affected by crescents, and mice had m arked azotemia and proteinuria, CD4 and combined CD4/CD8-deficient mic e developed minimal evidence of GN. On day 21, their glomeruli showed only mild proliferative changes and crescents, azotemia, and proteinur ia were absent. In contrast, CD8-deficient mice developed severe cresc entic GN with three of five mice dying on day 20 with ascites and edem a. The two mice surviving to day 21 had severe azotemia, Crescent deve lopment was accelerated (day 14, 51.6 +/- 2.4% of glomeruli; day 20 or 21, 62.0 +/- 4.0% of glomeruli), These studies demonstrate that CD4 c ells are crucial for the development of crescentic GN in mice and that genetic absence of CD8 cells accelerates disease. They support the hy pothesis that crescent formation is a manifestation of CD4-dependent ( wand CDS-independent) delayed type hypersensitivity in the glomerulus.