Intrathymic kidney cells delay the onset of lupus nephritis in MRL-lpr/lpr mice

Introduction of antigens to maturing T cells in the neonatal thymus is an effective means of inducing tolerance; however, it is uncertain whether developing, pathogenic, autoreactive T cells can be selectively modulated during systemic autoimmunity. To address this issue, syngeneic cells, derived from the kidneys of pre-diseased, lupus-prone, MRL-lpr/lpr mice were administered intrathymically to either neonatal or young MRL-lpr/lpr mice. For comparison, littermates were injected with splenocytes, islet cells or saline. Kidney cells administered to neonatal mice resulted in attenuation of nephritis, despite elevated serum autoantibody levels, IgG deposits and lymphadenopathy. This effect was not observed with administration of either the renal cell preparations to older mice or islet cells to younger mice, although splenocytes provided some benefit in younger mice. The results indicate that a subset of autoreactive T cells, distinct from those that augment autoantibody production and lymphadenopathy, are necessary for the expression of severe nephritis in MRL-lpr/lpr mice, and they provide further support for a renal antigen-specific component to the phenotype.