IMPAIRED RECOVERY AND CYTOLYTIC FUNCTION OF CD56-CELLS AND NON-T-CELLS IN SYSTEMIC LUPUS-ERYTHEMATOSUS FOLLOWING IN-VITRO POLYCLONAL T-CELLSTIMULATION - STUDIES IN UNSELECTED PATIENTS AND MONOZYGOTIC DISEASE-DISCORDANT TWINS( T)

Objective. To determine whether there is impaired generation and cytol ytic function of CD56+ T cells and non-T cells in human systemic lupus erythematosus (SLE). Methods. Peripheral blood mononuclear cells (PBM C) were obtained from 73 patients with SLE, 39 normal controls, and 9 pairs of monozygotic (MZ) twins discordant for SLE. PBMC were stimulat ed with anti-CD3 monoclonal antibody, maintained in interleukin-2, and assayed for percentages of total CD56+ cells and CD56+ T cells by flo w cytometry, and for cytolytic activity against Cr-51-labeled Daudi ta rget cells. Results. Despite normal total cell expansion, the percenta ges of recovered CD56+ T cells and total CD56+ cells were 1.6-fold and 1.8-fold lower, respectively, in patients with SLE compared with norm al controls (P = 0.011 and P < 0.001, respectively). Cytolytic activit ies of isolated total CD56+ cells and CD56+ T cells and were also redu ced in patients with SLE compared with normal controls (P = 0.033). Th ese defects associated with SLE were independent of disease activity a nd immunosuppressive medications, and they reflected impaired maturati on of cytolytic effector cells rather than a deficiency in precursor c ell number. In MZ twins discordant for SLE, recovered percentages of C D56+ cells and cytolytic responses were very low in 4 of 8 and 6 of 9 co-twins with SLE, respectively, Cell-mixing experiments with the PBMC of the MZ twins demonstrated that the E+ cell fractions (containing a ll T cells and CD56+ non-T cells) from the co-twins with SLE had decre ased ability to generate cytolytic activity compared with the correspo nding E+ cell fractions from the healthy co-twins. However, recovered percentages of CD56+ cells and non-T cells and cytolytic responses wer e also depressed in 4 of 8 and 4 of 9 healthy co-twins, respectively. Conclusion. Impaired CD56+ T cell and non-T cell responses are a featu re of SLE and may antedate the onset of clinical disease.