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Differences in the Age-Dependent Release of a Low Molecular Weight Suppressor (LMWS) and Stimulators by Normal and NZB/W Lymphoid Organs¹

Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, and The Arthritis and Rheumatism Branch, National Institute of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health, Bethesda, Maryland 20014

Abstract

The age-dependent release of soluble suppressors and stimulators of DNA synthesis by cultured thymocytes and spleen cells from C57BL/6 and BALB/c mice was compared with their release by NZB/W lymphoid organs. Spleen cells from the normal strains released high levels of suppressor early in life and gradually decreasing quantities with age. NZB/W spleen cells exhibited an early deficiency followed by a later excess in the production of suppressor. These differences were quantitated by dose-response studies. Thymocytes from the normal strains released stimulatory factors throughout life. In contrast, NZB/W thymocytes stopped releasing stimulatory activity and began to produce suppressor after 2 to 4 months of life. This abnormal elaboration of suppressor by thymocytes occurred 2 months before its reappearance in the autologous spleen cell supernatant. Both the early and late-appearing NZB/W suppressors were of low molecular weight (<1000). This activity was designed as low molecular weight suppressor (LMWS). Its aberrant production by the lymphoid organs of NZB/W mice correlated well with their reported functional immunologic abnormalities. The following items were discussed: the production of LMWS by adherent spleen cells, its relationship to previously described regulators, its partial purification and initial chemical characterization, and exclusion of the naturally occurring inhibitors of lymphocyte activation, cortisol, corticosterone, cold thymidine, and cyclic AMP as the active molecule.

Footnotes

¹ This study was supported in part by Grant CA15673, awarded by the National Cancer Institute, Department of Health, Education, and Welfare.