T‐cell receptor Vβ gene expression in experimental lupus nephritis

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Abstract
A limited T-cell receptor (TCR) Vβ repertoire employed by autoreactive T cells may be related to the development and course of autoimmune diseases. Vβ repertoire skewing has been observed not only in man, but also in animal models of several human autoimmune diseases, such as MRL-lpr mice, which spontaneously develop a systemic lupus erythematosus (SLE)-like disease. Murine chronic graft-versus-host disease (GVHD) is an inducible model for SLE, involving direct interaction between donor T cells and recipient B cells. It is not known whether Vβ-specific T-cell subsets are pathogenically involved in this model. Retroviral superantigens such as Mls-1 are known to have a profound impact on the TCR Vβ repertoire in mice. Restriction of the peripheral TCR repertoire may result from intrathymic expression of Mls-1, which causes deletion of T cells expressing Vβ6, -7, -8.1, or -9. Mls-1 incompatibility between donor and recipient can be used to determine the involvement of these TCR Vβ families in GVHD. In the present study we induced GVHD in several strain combinations to investigate TCR Vβ gene expression during GVHD, and the effect of Mls-1 incompatibility on the TCR Vβ repertoire. TCR Vβ gene expression was determined using an RNase protection assay. Our results indicate that T cells expressing the Vβ2 or Vβ16 chain play an important pathogenetic role, while T cells bearing the Vβ1 or Vβ6 chain may be related to self-limitation of the lupus-like disease in this model.