Genetic studies of autoimmunity and retrovirus expression in crosses of New Zealand black mice. II. The viral envelope glycoprotein gp70.

Datta, Somnath; McConahey, Patricia J.; Manny, Noga; Theofilopoulos, Argyrios N.; Dixon, Frank J.; Schwartz, Robert S.

doi:10.1084/jem.147.3.872

Cited by 55 publications

(22 citation statements)

References 16 publications

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“…31,32 Thus, all loci in the progeny from this cross bear at least 1 SWR allele (derived from the SWR parent), while the other allele is either SWR or NZB in origin, as it arises from the F1 parent. Mice were sero-tested at 9-12 months of age, or earlier if moribund.…”

Section: Mice and Phenotypingmentioning

confidence: 99%

Dominant NZB contributions to lupus in the (SWR×NZB)F1 model

et al. 2002

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Section: Mice and Phenotypingmentioning

confidence: 99%

Dominant NZB contributions to lupus in the (SWR×NZB)F1 model

et al. 2002

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“…This animal had been tested virologically twice, at 3 mo of age and again at 14 mo of age, and on both occasions no virus was detected. The level of gp70 in the serum of this mouse was elevated (15.7 ~g/ml); this subject will be dealt with in the succeeding paper (8).…”

Section: °I I • ~30mentioning

confidence: 99%

Genetic studies of autoimmunity and retrovirus expression in crosses of New Zealand black mice I. Xenotropic virus.

Datta

Manny

Andrzejewski

et al. 1978

The Journal of Experimental Medicine

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Type C RNA viruses (retroviruses) have been implicated in the autoimmune disease of New Zealand Black (NZB) 1 mice (1, 2). However, the evidence for this is only circumstantial because the retroviruses isolated from NZB mice are xenotropic in host range; this prohibits a direct test of their pathogenicity in mice by, for example, inoculation of filtrates (3, 4). Nevertheless, the relationship between autoimmunization and xenotropic viruses c&n be ascertained by genetic tests because the genes of these agents are an integral part of cellular chromosomes (5) and their expression in NZB mice is governed by two autosomal dominant genes (6, 7). In this paper we describe results of genetic experiments designed to test the hypothesis that expression of xenotropic virus is required for the development of autoimmune disease. The following paper (8) deals with the relationship between autoimmune disease in NZB mice and expression of the major envelope glycoprotein of the virus, gp70. Materials and MethodsMice. NZB, SWR, C57BL/6, B10.A, and AKR mice were obtained from The Jackson Laboratory, Bar Harbor, Maine. Reciprocal crosses were made to produce FI and backcross progeny mice. Because the maternal direction of the cross did not affect the results, all data for a given cross were pooled and presented by a single nomenclature: F~ for (SWR × NZB)F~; (F~ × SWR) for backcross to SWR, and (F~ x NZB) for backcross to NZB. The mice were 11-24 mo old when tested.Retrovirus Assays XI~.NOTROPIC VIRUS. Spleen cell suspensions were prepared and serially diluted as described previously (6, 7, 9). They were assayed by cocultivation on monolayers of the feline 81 cell line

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“…In addition, we examined the effects of treatment with a COX-2 inhibitor diet on spontaneously developing SLE in SNF 1 mice (17,18).…”

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Hyperexpression of cyclooxygenase 2 in the lupus immune system and effect of cyclooxygenase 2 inhibitor diet therapy in a murine model of systemic lupus erythematosus

Zhang

Bertucci

Smith

et al. 2007

Arthritis & Rheumatism

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Objective. To investigate the role of cyclooxygenase 2 (COX-2) in the functioning of different cell types involved in the lupus autoimmune response, and to examine the therapeutic effect of COX-2 inhibitors in mice prone to spontaneously develop systemic lupus erythematosus (SLE).Methods. Lupus-prone (SWR ؋ NZB)F 1 mice were fed with a diet containing different doses of the COX-2-specific inhibitor celecoxib or the nonspecific inhibitor aspirin, or a combination of both, and the effects of the therapy on autoantibody production, development of lupus nephritis, and mortality were determined. Expression of COX-2 by different cells of the lupus immune system and the effect of COX-2 inhibitors on the function of these cells in vitro and in vivo were assessed.Results. The immune cells of mice with SLE spontaneously hyperexpressed COX-2, and COX-2 inhibitors could cause cell apoptosis. Treatment with COX-2 inhibitors resulted in decreased autoantibody production and inhibition of the T cell response to the major lupus autoantigen, nucleosome, and its presentation by antigen-presenting cells. Surprisingly, a significant increase in survival occurred only in mice receiving intermittent therapy with the lowest dose of celecoxib (500 parts per million), approximating <100 mg of celecoxib/day in humans. A continuous diet, but not intermittent feeding, with the combination of celecoxib and aspirin delayed development of nephritis temporarily, but failed to prolong survival. Indeed, treatment with aspirin alone increased mortality.Conclusion. The contributions of the major players in the pathogenic autoimmune response, namely, T cells, B cells, dendritic cells, and macrophages that are abnormally hyperactive in lupus, depend on the increased expression and activity of COX-2, similar to inflammatory cells in target organs. Intermittent pulse therapy with low doses of select COX-2 inhibitors would be of value in the treatment of lupus.In systemic lupus erythematosus (SLE), hyperactivity of the immune system leads to activation of certain autoimmune T helper cells, which drive autoimmune B cells to produce somatically mutated IgG autoantibodies against apoptotic nuclear antigens (1-6). IgG immune complexes containing autoantigenic DNA and RNA bind Fc␥ receptors and Toll-like receptors (TLRs), which results in stimulation of type I interferon (IFN) production by hyperactive dendritic cells (DCs); moreover, autoimmune B cells bearing the T helper celldriven, high-affinity, somatically mutated B cell receptors are dually stimulated by TLRs (7-9). These events further amplify the ability of antigen-presenting cells (APCs) to present autoantigens to pathogenic T helper cells, which is an essential element of disease development (10-13).Normally, autoreactive T and B cells are eliminated by functional inactivation (anergy) and by activation-induced cell death (AICD; apoptosis), via Fas signaling (14). However, autoimmune T helper cells in human lupus resist AICD by up-regulating the expression of cyclooxygenase 2 (COX-2) and the anti...

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Genetic studies of autoimmunity and retrovirus expression in crosses of New Zealand black mice. II. The viral envelope glycoprotein gp70.

Cited by 55 publications

References 16 publications

Dominant NZB contributions to lupus in the (SWR×NZB)F1 model

Dominant NZB contributions to lupus in the (SWR×NZB)F1 model

Genetic studies of autoimmunity and retrovirus expression in crosses of New Zealand black mice I. Xenotropic virus.

Hyperexpression of cyclooxygenase 2 in the lupus immune system and effect of cyclooxygenase 2 inhibitor diet therapy in a murine model of systemic lupus erythematosus

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