Costimulatory molecules CD80 and CD86 in human crescentic glomerulonephritis

Background: CD80 and CD86, cell-surface molecules found only on antigen-presenting cells (APCs), are required for activation of CD4-postitve (CD4(+)) T cells by interaction with CD28/cytotoxic T-lymphocyte-associated antigen 4 on T cells. The roles of these molecules in human glomerulonephritis (GN) presently are unknown. Methods:Twelve cases of crescentic GN, thought to be a T helper cell-directed delayed-type hypersensitivity-like injury, and 10 controls with non-immunoglobulin A proliferative GN were used. Expression of CD80, CD86, CD4, CD14, CD68, HLA-DR, and intercellular adhesion molecule-1 was investigated in renal tissues using monoclonal antibodies and compared with clinical data at the time of renal biopsy. Results: CD80(+) and CD86(+) cells were observed significantly more in crescentic GN than in controls. CD86 was expressed in the glomerulus and interstitium, especially in the crescent, and adhesion to Bowman's capsule and periglomerular areas corresponding to these changes. Tubular epithelial cells showed no CD86 expression, but they expressed CD80, and some of them expressed HLA-DR. CD4, CD14, CD68, and CD86 showed similar distribution patterns. Positive correlations were found between CD86+ cells and CD4(+), CD14(+), and CD68(+) cells. The number of interstitial CD86+ cells correlated with deterioration of renal function. Most CD86(+) cells were monocyte/macrophages. Conclusion: This study suggests that the costimulatory molecules CD80 and CD86 have different expressions in human crescentic GN, and CD86 is concerned with crescent formation and CD4(+) T-cell accumulations. The majority of APCs are macrophages, and tubular cells also can act as APCs.