title: beta2-microglobulin dependence of the lupus-like autoimmune syndrome of MRL-lpr mice.
abstract: MRL-lpr/lpr mice develop a distinctive immunologic disease characterized by accumulation of unusually large numbers of T cells in the peripheral lymphoid organs. Most of the accumulating T cells express an alpha beta-TCR but are peculiar in that they express neither CD4 nor CD8 co-ligands. Concurrent with lymphoaccumulation of such double negative (DN) T cells, MRL-lpr/lpr mice develop a lethal systemic lupus erythematosus-like autoimmune syndrome. This study focuses on the role of MHC class I molecules in this latter pathologic process. Highly backcrossed class I molecule-deficient MRL and MRL-lpr mice carrying a functionally defective allele of the gene beta 2-microglobulin (B2m) were produced. Class I deficient MRL-lpr/lpr mice demonstrated a substantial reduction in DN T cells, confirming other reports indicating that most DN T cells arise from progenitors positively selected on MHC class I molecules. Significantly, class I-deficient MRL-lpr/lpr mice also demonstrated a diminution of every autoimmune disease indicator analyzed including hypergammaglobulinemia; autoantibodies including anti-DNA, anti-Smith antigen, and rheumatoid factor; and glomerulonephritis. The results indicate that class I-dependent T cells are crucial not only for the development of DN T cells, but for multiple features of the MRL-lpr/lpr systemic lupus erythematosus syndrome. Moreover, the pattern of hypergammaglobulinemia suggests that the requirement for MHC class I proteins is restricted temporally to later stages of the disease.
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Christianson
authors.forename: R L
authors.initials: RL
authors.lastname: Blankenburg
authors.forename: T M
authors.initials: TM
authors.lastname: Duffy
authors.forename: D
authors.initials: D
authors.lastname: Panka
authors.forename: J B
authors.initials: JB
authors.lastname: Roths
authors.forename: A
authors.initials: A
authors.lastname: Marshak-Rothstein
authors.forename: D C
authors.initials: DC
authors.lastname: Roopenian
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013577:Syndrome; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013997:Time Factors; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000276:immunology*
chemical_list: D017931:DNA Primers; D015395:Histocompatibility Antigens Class I; D016693:Receptors, Antigen, T-Cell, alpha-beta; D001613:beta 2-Microglobulin