HIGH LEVELS OF BCL-2 PROTEIN IN CIRCULATING T-LYMPHOCYTES, BUT NOT B-LYMPHOCYTES, OF PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS

Objective. Defective regulation of programmed cell death (apoptosis) m ay play a role in the development of autoimmune diseases, and the prot o-oncogene bcl-2 is involved in the control of apoptosis in immunocomp etent cells. We therefore wished to investigate the expression of bcl- 2 in the peripheral lymphocytes of patients with systemic lupus erythe matosus (SLE), a prototypical autoimmune disease. Methods. Levels of b cl-2 expression in the lymphocytes of patients with SLE and, for compa rison, in the lymphocytes of healthy controls and patients with rheuma toid arthritis (RA), systemic bacterial infections, and chronic B cell lymphocytic leukemia were studied by 2-color cytofluorography and RNA analysis. Results. In SLE patients, a significant proportion of T cel ls expressed increased amounts of bcl-2 protein. By fluorescence-activ ated cell sorter analysis, bcl-2-enriched lymphocytes were found in th e CD45RO+ as well as in the CD45RO-, and also in the CD4+ and CD8+, ly mphocyte subpopulations. Mononuclear cells of patients with SLE showed increased amounts of bcl-2 messenger RNA. An increased percentage of strongly bcl-2 positive peripheral T lymphocytes was found in patients with bacterial infections, but not in those with RA. Conclusion. Alth ough the occurrence of circulating T lymphocytes with abnormally high bcl-2 expression is not specific for SLE, it is evidence for a dysregu lation of lymphocytic programmed cell death in this autoimmune disease .