Quantitative and qualitative analysis of the balance between type 1 and type 2 cytokine-producing CD8(-) and CD8(+) T cells in systemic lupus erythematosus.
The production of type 1 (IFN-gamma, IL-2) and type 2 (IL-4, IL-5, IL-10, IL-13) cytokines by CD8(-) and CD8(+) T cells from systemic lupus erythematosus (SLE) patients and normal subjects was investigated using an intracellular cytokine-staining technique. This flow cytometric method facilitates analysis of both surface markers and cytoplasmic cytokines, after a short term (6 h) culture with or without phorbol myristate acetate and ionomycin (PMA/I) stimulation. In SLE patients, more unstimulated T cells produced IL-10 in comparison with controls; other cytokines were not detected in unstimulated cells. The percentage of IL-10-secreting T cells did not significantly increase after PMA/I stimulation of cells from SLE patients. The mean intensity of fluorescence (MIF) of intracellular IL-4 staining was significantly higher in CD8(-) T cells of SLE patients than controls. Significantly fewer CD8(-) and CD8(+) T cells from SLE patients secreted IFN-gamma after PMA/I stimulation compared with controls. The MIF and percentage of IL-2, IL-5, and IL-13-secreting cell subsets were not significantly different between SLE patients and controls. These findings indicate that T cells of SLE patients are already stimulated to produce IL-10 in vivo, which may result in downregulation of IFN-gamma secreting CD8(-) and CD8(+) T cells observed following PMA/I stimulation. Thus, the population size of Th1 and Tc1 cells are reduced in SLE patients whereas the effector function of Th2 cells, with respect to IL-4 production, is enhanced in SLE patients. Furthermore, although the balance between Th1/Th2 and between Tc1/Tc2 is disrupted in SLE patients, it is significantly biased in favour of the Th2 subset only.
Amel-Kashipaz
M R
MR
Division of Molecular and Clinical Immunology, School of Clinical Laboratory Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, UK. nixmra@nottingham.ac.uk
Huggins
M L
ML
Lanyon
P
P
Robins
A
A
Todd
I
I
Powell
R J
RJ
D000328:Adult; D000368:Aged; D016827:CD8 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018793:Interleukin-13 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013194:Staining and Labeling; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism*
D016827:CD8 Antigens; D016207:Cytokines; D018793:Interleukin-13; D007376:Interleukin-2; D015848:Interleukin-5; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma