T-cell receptor Vbeta gene expression in experimental lupus nephritis.
A limited T-cell receptor (TCR) Vbeta repertoire employed by autoreactive T cells may be related to the development and course of autoimmune diseases. Vbeta 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 Vbeta-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 Vbeta repertoire in mice. Restriction of the peripheral TCR repertoire may result from intrathymic expression of Mls-1, which causes deletion of T cells expressing Vbeta6, -7, -8.1, or -9. Mls-1 incompatibility between donor and recipient can be used to determine the involvement of these TCR Vbeta families in GVHD. In the present study we induced GVHD in several strain combinations to investigate TCR Vbeta gene expression during GVHD, and the effect of Mls-1 incompatibility on the TCR Vbeta repertoire. TCR Vbeta gene expression was determined using an RNase protection assay. Our results indicate that T cells expressing the Vbeta2 or Vbeta16 chain play an important pathogenetic role, while T cells bearing the Vbeta1 or Vbeta6 chain may be related to self-limitation of the lupus-like disease in this model.
Department of Pathology, Leiden University Hospital, The Netherlands.
M
M
Sutmuller
H J
HJ
Baelde
S
S
Ouellette
E
E
De Heer
J A
JA
Bruijn
D000818:Animals; D001947:Breeding; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D019674:Genes, T-Cell Receptor beta; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology; D007150:Immunohistochemistry; D008181:Lupus Nephritis / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D016747:Minor Lymphocyte Stimulatory Antigens / Q000276:immunology; D012313:RNA / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism*
D016747:Minor Lymphocyte Stimulatory Antigens; D012313:RNA