Treatment of NZB/NZW mice with total lymphoid irradiation: long-lasting suppression of disease without generalized immune suppression.

Abstract

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.

• Authors: B L Kotzin, R Arndt, S Okada, R Ward, A B Thach, S Strober
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 136 Issue 9 Pg. 3259-65 (May 01 1986) ISSN: 0022-1767 [Print] United States
• PMID: 2937842 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Immunoglobulin Allotypes
• Lipopolysaccharides
• Phytohemagglutinins

Topics

• Animals
• Antibody-Producing Cells (metabolism)
• Autoimmune Diseases (immunology, physiopathology)
• B-Lymphocytes
• Female
• Immunoglobulin Allotypes (biosynthesis)
• Immunosuppression Therapy (methods)
• Leukocyte Count (radiation effects)
• Lipopolysaccharides (pharmacology)
• Lymphocyte Activation
• Lymphocyte Culture Test, Mixed
• Mice
• Mice, Inbred BALB C
• Mice, Inbred NZB
• Phytohemagglutinins (pharmacology)
• Spleen
• T-Lymphocytes
• Time Factors
• Whole-Body Irradiation