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Impairment of CD8⁺ T Suppressor Cell Function in Patients with Active Systemic Lupus Erythematosus¹

Department of Internal Medicine, Division of Internal Medicine and Clinical Immunology, University of Genoa, Genoa, Italy

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- 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- 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.

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