beta2-microglobulin dependence of the lupus-like autoimmune syndrome of MRL-lpr mice.
Animal, Autoimmune-Diseases: im, Base-Sequence, DNA-Primers, Histocompatibility-Antigens-Class-I: im, Lupus-Erythematosus-Systemic: im, Mice, Mice-Mutant-Strains, Molecular-Sequence-Data, Receptors-Antigen-T-Cell-alpha-beta: im, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S, Syndrome, T-Lymphocyte-Subsets: im, Time-Factors
J Immunol 1996 Jun 15;156(12):4932-9
AI28802/AI/NIAID, AI24544/AI/NIAID, P40
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.
Christianson, G J.; Blankenburg, R L.; Duffy, T M.; Panka, D; Roths, J B.; Marshak, Rothstein A.; and Roopenian, D C., " beta2-microglobulin dependence of the lupus-like autoimmune syndrome of MRL-lpr mice." (1996). Faculty Research 1990 - 1999. 828.