Treatment of NZB/NZW mice with total lymphoid irradiation: long-lasting suppression of disease without generalized immune suppression
We used total lymphoid irradiation (TLI; total dose = 3400 rad) to treat the lupus-like renal disease of 6-mo-old female NZB/NZW mice. Similar to our past studies, this treatment resulted in a marked prolongation of survival, decrease in proteinuria, and decrease in serum anti-DNA antibodies compared with untreated littermate controls. Although there was no evidence of disease recurrence in TLI-treated mice until after 12 mo of age, the in vitro proliferative response to phytohemagglutinin by NZB/NZW spleen cells recovered within 6 wk such that responses were greater than control NZB/NZW animals. A similar recovery and overshoot after TLI were evident in the primary antibody response to the T cell-dependent antigen sheep red blood cells (SRBC). Both the total and IgG anti-SRBC antibody responses after TLI were greater than those of untreated NZB/NZW controls, and were comparable with those of untreated non-autoimmune mice. Despite this increased response to mitogens and antigens after TLI, we noted a decrease in spontaneous splenic IgG-secreting cells and a decrease in IgG but not IgM antinuclear antibody production. Nonspecific suppressor cells of the mixed leukocyte response were detectable in the spleens of NZB/NZW mice early after TLI. However, the disappearance of suppressor cells was not associated with recrudescence of disease activity. Furthermore, transfer of large numbers of spleen cells from TLI-treated NZB/NZW mice did not result in disease suppression in untreated age-matched recipients. In summary, treatment of NZB/NZW mice with TLI results in a prolonged remission in autoimmune disease, which is achieved in the absence of generalized immunosuppression.
- Research Organization:
- V.A. Medical Center, Denver, CO
- OSTI ID:
- 5804066
- Journal Information:
- J. Immunol.; (United States), Vol. 9
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
LYMPHOCYTES
IRRADIATION
UROGENITAL SYSTEM DISEASES
IMMUNOSUPPRESSION
ANTIGEN-ANTIBODY REACTIONS
CELL PROLIFERATION
LIPOPOLYSACCHARIDES
MICE
PHYTOHEMAGGLUTININ
RADIATION DOSES
SPLEEN CELLS
SURVIVAL TIME
AGGLUTININS
ANIMAL CELLS
ANIMALS
ANTIBODIES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOHYDRATES
CONNECTIVE TISSUE CELLS
DISEASES
DOSES
HEMAGGLUTININS
LEUKOCYTES
LIPIDS
MAMMALS
MATERIALS
MITOGENS
MUCOPROTEINS
ORGANIC COMPOUNDS
POLYSACCHARIDES
PROTEINS
RODENTS
SACCHARIDES
SOMATIC CELLS
VERTEBRATES
560121* - Radiation Effects on Cells- External Source- (-1987)
550901 - Pathology- Tracer Techniques