CD8alpha+beta(low) effector T cells in systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by the loss of self-tolerance to nuclear antigens. Aberrant T-cell function plays a central role in lupus pathogenesis. We and others previously demonstrated that peripheral TCRalphabeta+CD3+ T cells express CD8beta either at a high (CD8beta(high)) or low density (CD8beta(low)), thereby defining two functionally distinct subsets. CD8beta(low) T cells express predominantly CD8alphaalpha and less CD8alphabeta as a coreceptor, display a differentiated phenotype and exert effector function. CD8beta(high) T cells appear to be the precursors expressing predominantly the heterodimeric efficient CD8alphabeta coreceptor, exhibiting a naïve phenotype and high proliferative capacity. In the present study, the distribution and functional properties of CD8beta(high) and CD8beta(low) T cells of SLE patients were compared (n = 20) with those of healthy subjects (n = 16). It was found that expansion of CD8beta(low) T-cell subset correlated with disease activity indicating chronic antigenic stimulation leading to a major lack of naïve CD8beta(high) precursor T cells in SLE. Functional characteristics of CD8beta(low) T cells including production of cytokines and cytotoxic granules were not significantly different between patients with SLE and healthy individuals. We speculate that unbalanced CD8beta(high)/CD8beta(low) T-cell relation reflects a skewed homeostasis within the CD8+ T-cell compartment towards fully differentiated effector T cells possibly due to persistent antigen stimulation in SLE.
Werwitzke
S
S
Clinic for Immunology and Rheumatology, Hannover Medical School, Hannover, Germany.
Tiede
A
A
Jacobs
R
R
Zielinska-Skowronek
M
M
Buyny
S
S
Schmidt
R E
RE
Witte
T
T
D017252:CD3 Complex / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D003594:Cytoplasmic Granules / Q000378:metabolism; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000276:immunology*; D018655:Lymphocyte Count; D054504:Precursor Cells, T-Lymphoid / Q000166:cytology / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D017252:CD3 Complex; D016827:CD8 Antigens; C433839:CD8alphabeta antigen; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta