Glomerular T cells in Heymann nephritis

Abstract

Summary Active Heymann nephritis (HN) is a rat model of human membranous nephropathy. The appearance of T cells within the glomeruli of HN rats suggests a role for these cells in the pathogenesis of the disease. The aims of this study were to investigate T cells infiltrating the glomerulus in HN in Lewis rats by polymerase chain reaction (PCR) of their Vβ chains, CDR3 spectratyping and sequencing. HN was induced in Lewis rats by immunization with renal tubular antigen (Fx1A) in CFA. Kidneys were collected between 4 and 10 weeks. The glomeruli were separated, homogenized and RNA extracted. RT-PCR, CDR3 spectratyping and sequencing were used to further characterize the infiltrating T cells. Multiple Vβ families showed restriction of their CDR3 spectratypes in each animal. Several TCR Vβ families had identical-sized restricted spectratypes across several different animals. Four Vβ families were sequenced. In three of those four families, the dominant clones showed identical sized CDR3 regions and a striking over-expression of Jβ2.6. Further analysis of the CDR3 regions of the Jβ2.6 clones showed a significant restriction of the amino acids at four of the six CDR3 positions. Glomerular T cells bearing similar CDR3 sequences, using Jβ2.6 and expressing at least two, and possibly more, Vβ genes are involved in the pathogenesis of HN.