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.


CONCLUSIONS
Impaired CD56+ T cell and non-T cell responses are a feature of SLE and may antedate the onset of clinical disease.
Division of Rheumatology and Immunology, University of Southern California, Los Angeles 90033, USA.
W
W
Stohl
J E
JE
Elliott
A S
AS
Hamilton
D M
DM
Deapen
T M
TM
Mack
D A
DA
Horwitz
D000328:Adult; D017252:CD3 Complex / Q000032:analysis; D019002:CD56 Antigen / Q000032:analysis*; D004200:Diseases in Twins / Q000235:genetics*; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D014430:Twins, Monozygotic
D017252:CD3 Complex; D019002:CD56 Antigen