Adjuvant effects on poly I poly C in New Zealand mice

Genetic, environmental, and immune factors have been implicated in the pathogenesis of active systemic lupus erythematosus (SLE). To investigate the basis for abnormalities in immune regulation, we studies lymphocytes from patients with SLE during the active and inactive phases of their disease to examine their ability to develop Con A induced suppressor function (5 patients) and to develop a normal autologous mixed lymphocyte reaction (MLR) (7 patients). In each case results of these in vitro tests using whole T cells were abnormal during the active phase of the disease and returned to normal when the disease activity decreased. The results of this study suggest that the abnormalities of suppressor cell generation and the autologous MLR observed in whole T cell populations from patients with active SLE are not solely due to intrinsic and invariant lymphocyte defects. They further suggest that loss of immune regulatory function is not a simple genetically determined trait since the regulatory function returned to normal when the disease became inactive. However, these results do not exclude an underlying genetic effect on the immune system which requires a second factor (such as an environmental trigger) for expression. Evidence in support of this latter possibility derives from studies of Tγ cells. Fractionation of the functionally normal whole T cells from some patients who were clinically inactive revealed impaired function of Tγ cells. This subset of T cells may be easily perturbed by stimuli not sufficient to cause clinically apparent disease.

Section: Discussionmentioning

confidence: 99%

Studies of immune functions of patients with systemic lupus erythematosus

Sakane

Green

1980

“…Antibodies to SRBC and to SSSZII (subject to macrophage and helper T cell control and suppressor T cell control, respectively) were measured by enumerating plaque forming cells in spleens from immunized mice by incubating these cells with SRBC or SSSIII coated SRBC, as described previously (16,18,19).…”

Section: Methodsmentioning

confidence: 99%

Alteration of lymphocyte function in nzb/nzw mice

Hahn

Knotts

1979

NZB/NZW F1 female mice received levamisole in an attempt to increase suppressor T cell function. Responses varied with dosage of drug and age of mice. When treatment with 25 μg/gm doses (intermittent or daily) was begun at 12 weeks of age, nephritis was accelerated in spite of transient reduction of anti‐DNA antibodies. When treatment was begun at 4 weeks, or when doses of 250 μg/gm were given, no clinical effects were observed. In the mice with accelerated disease, delayed hypersensitivity and antibody responses to sheep erythrocytes increased; antibody responses to pneumococcal poiysaccharide were unaffected. It is possible that some increased immune responses associated with levamisole are undesirable in murine lupus.

“…Measurements of spleen PFC after immunization with SRBC were performed by using a modified Jerne assay, as described by Jacobs and colleagues (21). Mice were inoculated with 3 X 10' SRBC intravenously and spleens were assayed for PFC on day 4, which was the day of maximal response.…”

Section: Test Proceduresmentioning

confidence: 99%

Effect of altered lymphocyte function on immunologic disorders in nzb/nzw mice

Mehta

Knotts

Hahn

1977

NZB/NZW F, female mice were treated with the immunosuppressive enzyme L-asparaginase ( Asnase) for up to 32 weeks. Asnase diminished circulating anti-DNA and antinuclear antibodies, diminished deposition of yglobulins in kidneys, significantly delayed the onset of proteinuria, and reduced deaths from nephritis. These effects were associated with reduction of cellular IgM antibody synthesis to both T-dependent and T-independent antigens, but the graft-versus-host reaction was not affected. After several weeks of therapy, antibodies against Asnase appeared in the circulation, the effect od antibody synthesis was lost, ANA and anti-DNA appeared, followed by proteinuria and deaths from nephritis. Therefore Asnase proved to be an effective therapy in NZB/NZW mice, but its usefulness was limited by the appearance of inactivating antibodies. NZB/NZW F, mice develop lethal immune complex glomerulonephritis accompanied by antibodies to