The purpose of this paper is to analyze the relationship between alterations of splenic T-cell subpopulations and the amelioration of autoimmune diseases of MRL/MpTn-gld/gld mice (MRL/gld mice) after extended exposure to low-dose radiation. After the onset of disease, 4-month-old MRL/gld mice were exposed to doses of 0.05, 0.2, and 0.5 Gy/day for 4 weeks (5 days/week), for total doses of 1, 4, ...

Autoimmune lupus nephritis is dependent on infiltrating autoreactive leukocytes and Igs. B7 costimulatory molecules (B7-1 and B7-2) provide signals essential for T cell activation and Ig class switching. In MRL-Faslpr mice, a model of human lupus, although multiple tissues are targeted for autoimmune injury, nephritis is fatal. We identified intrarenal B7-1 and B7-2 expression, restricted to ki...

B cells are required for both the expression of lupus nephritis and spontaneous T cell activation/memory cell accumulation in MRL-Faslpr mice (MRL/lpr). Autoimmunity in the MRL/lpr strain is the result of Fas-deficiency and multiple background genes; however, the precise roles of background genes vs Fas-deficiency have not been fully defined. Fas-deficiency (i.e., the lpr defect) is required in...

MRL/MpJ-Fas lpr/lpr /J (MRL lpr) mice develop lupus-like disease manifestations in an IL-21–dependent manner. IL-21 is a pleio-tropic cytokine that can influence the activation, differentiation, and expansion of B and T cell effector subsets. Notably, auto-reactive CD4 + T and B cells spontaneously accumulate in MRL lpr mice and mediate disease pathogenesis. We sought to identify the particular...

Complement factor H (CfH) is a key regulator of the alternative pathway, and its presence on mouse platelets and podocytes allows the processing of immune complexes. Because of the role of immune complexes in the pathophysiology of lupus nephritis, we studied the role of CfH in the development of nephritis in MRL-lpr mice, an animal model of lupus. At 12 weeks, CfH-deficient MRL-lpr mice had si...

Cell-based therapies, using multipotent mesenchymal stem cells (MSCs) for organ regeneration, are being pursued for cardiac disease, orthopedic injuries and biomaterial fabrication. The molecular pathways that regulate MSC-mediated regeneration or enhance their therapeutic efficacy are, however, poorly understood. We compared MSCs isolated from MRL/MpJ mice, known to demonstrate enhanced regene...

The autoimmune-prone MRL-lpr substrain of mice develop an autoimmunity-associated behavioral syndrome (AABS) which resembles in many respects the behavior of animals exposed to chronic stress. The present study examined whether these mice show changes in the morphology of neuronal dendrites, as found in animals exposed to chronic stress. A modified Golgi-Cox procedure was used to visualize the ...

Hydrocephalus is an intractable disease characterized by the excessive accumulation of cerebrospinal fluid (CSF) in the cerebral ventricles. There are many cases in both human and animals; however, the cause and mechanism of it's development is not clearly understood. In this study, differences of cerebral ventricles in 5 inbred mice strains (MRL/MpJ, C57BL/6, C3H/He, DBA/2 and BALB/c) were inv...

Posttranslational protein modifications influence a number of immunologic responses ranging from intracellular signaling to protein processing and presentation. One such modification, termed isoaspartyl (isoAsp), is the spontaneous nonenzymatic modification of aspartic acid residues occurring at physiologic pH and temperature. In this study, we have examined the intracellular levels of isoAsp r...

Nitric oxide (NO) is an important mediator of the inflammatory response. MRL-lpr/lpr mice overexpress inducible nitric oxide synthase (NOS2) and overproduce NO in parallel with the development of an autoimmune syndrome with a variety of inflammatory manifestations. In previous studies, we showed that inhibiting NO production with the nonselective nitric oxide synthase (NOS) inhibitor NG-monomet...