Impaired recovery and cytolytic function of CD56+ T and non-T cells in systemic lupus erythematosus following in vitro polyclonal T cell stimulation. Studies in unselected patients and monozygotic disease-discordant twins.

OBJECTIVE

To determine whether there is impaired generation and cytolytic function of CD56+ T cells and non-T cells in human systemic lupus erythematosus (SLE).

METHODS

Peripheral blood mononuclear cells (PBMC) were obtained from 73 patients with SLE, 39 normal controls, and 9 pairs of monozygotic (MZ) twins discordant for SLE. PBMC were stimulated with anti-CD3 monoclonal antibody, maintained in interleukin-2, and assayed for percentages of total CD56+ cells and CD56+ T cells by flow cytometry, and for cytolytic activity against 51Cr-labeled Daudi target cells.

RESULTS

Despite normal total cell expansion, the percentages 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 normal controls (P = 0.011 and P < 0.001, respectively). Cytolytic activities of isolated total CD56+ cells and CD56+ T cells and were also reduced in patients with SLE compared with normal controls (P = 0.033). These defects associated with SLE were independent of disease activity and immunosuppressive medications, and they reflected impaired maturation of cytolytic effector cells rather than a deficiency in precursor cell number. In MZ twins discordant for SLE, recovered percentages of CD56+ cells and cytolytic responses were very low in 4 of 8 and 6 of 9 co-twins with SLE, respectively. Cellmixing experiments with the PBMC of the MZ twins demonstrated that the E+ cell fractions (containing all T cells and CD56+ non-T cells) from the co-twins with SLE had decreased ability to generate cytolytic activity compared with the corresponding E+ cell fractions from the healthy co-twins. However, recovered percentages of CD56+ cells and non-T cells and cytolytic responses were 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 feature of SLE and may antedate the onset of clinical disease.