Impairment of CD8(+) T suppressor cell function in patients with active systemic lupus erythematosus

Alteration of T cell suppression function has been recognized in patients w ith systemic lupus erythematosus (SLE). Recently, CD8(+) T suppressor lymph ocytes (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 fr om 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 proli feration of autologous PBMC, whereas CD8(+) Ts from SLE patients in remissi on exerted an inhibitory activity comparable to normal subjects. The inhibi tory effect of CD8(+) Ts cells was neither mediated by cytotoxic activity n or 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 CD 8(+) Ts suppression activity was obtained by blocking IFN-gamma with a spec ific Ab or by inhibiting CD8(+) Ts-mediated IL-6 secretion by an antisense oligonucleotide. Interestingly, CD8(+) Ts from SLE patients showed a peculi ar cytokine pattern characterized by an impaired secretion of IL-6 and an i ncreased secretion of IL-12. Thus, it appears that an altered balance betwe en inhibitory (IL-6) and stimulatory (IL-12) cytokines might be responsible for the functional impairment of CD8(+) Ts in SLE patients.