Impairment of CD8+ T Suppressor Cell Function in Patients with Active Systemic Lupus Erythematosus

• Published in: The Journal of immunology (1950) 2001-05, Vol.166 (10), p.6452-6457
• Main Authors: Filaci, Gilberto, Bacilieri, Sabrina, Fravega, Marco, Monetti, Monia, Contini, Paola, Ghio, Massimo, Setti, Maurizio, Puppo, Francesco, Indiveri, Francesco
• Format: Article
• Language: English
• Subjects: Adult; Antibodies, Monoclonal - pharmacology; CD3 Complex - immunology; Cell-Free System - immunology; Cells, Cultured; Coculture Techniques; Cytokines - biosynthesis; Down-Regulation - immunology; Female; Humans; Immunophenotyping; Interleukin-12 - biosynthesis; Interleukin-6 - antagonists & inhibitors; Interleukin-6 - biosynthesis; K562 Cells; Leukocytes, Mononuclear - immunology; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - pathology; Lymphocyte Activation - immunology; Male; Middle Aged; Solubility; Suppressor Factors, Immunologic - physiology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; T-Lymphocytes, Regulatory - pathology; Up-Regulation - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.166.10.6452

Alteration of T cell suppression function has been recognized in patients with systemic lupus erythematosus (SLE). Recently, CD8(+) T suppressor lymphocytes (CD8(+) Ts) have been generated in vitro by incubating purified CD8(+) T cells with IL-2 and GM-CSF. Using this method, we generated CD8(+) Ts from patients affected by SLE. No major differences were found in the CD8(+) Ts phenotype between SLE patients and healthy subjects. CD8(+) Ts from SLE patients with active disease did not inhibit the anti-CD3 mAb-induced proliferation of autologous PBMC, whereas CD8(+) Ts from SLE patients in remission exerted an inhibitory activity comparable to normal subjects. The inhibitory effect of CD8(+) Ts cells was neither mediated by cytotoxic activity nor by apoptosis induction. Two cytokines, IFN-gamma and IL-6, were found to be responsible for the function of CD8(+) TS: In fact, counteraction of CD8(+) Ts suppression activity was obtained by blocking IFN-gamma with a specific Ab or by inhibiting CD8(+) Ts-mediated IL-6 secretion by an antisense oligonucleotide. Interestingly, CD8(+) Ts from SLE patients showed a peculiar cytokine pattern characterized by an impaired secretion of IL-6 and an increased secretion of IL-12. Thus, it appears that an altered balance between inhibitory (IL-6) and stimulatory (IL-12) cytokines might be responsible for the functional impairment of CD8(+) Ts in SLE patients.