Impaired cytotoxic T lymphocyte activity in systemic lupus erythematosus following in vitro polyclonal T cell stimulation: a contributory role for non-T cells

To determine whether non-T cells contribute to impaired generation of nonre stricted cytotoxic T lymphocyte (CTL) activity in human SLE, peripheral blo od mononuclear cells (PBMC) and sort-purified T cells from normal subjects and SLE patients were stimulated with anti-CD3 mAb, maintained in IL2, and assayed for cytolytic activity against Cr-51-labeled Daudi target cells. In addition, T cell and non-T cell fractions were isolated from nine pairs of monozygotic (MZ) twins discordant for SLE, reconstituted in a criss-cross pattern, and stimulated and assayed for cytolytic activity. Cytolytic respo nses were significantly lon er in SLE PBMC cultures than in normal PBMC cul tures. Addition of SLE serum to normal PBMC cultures did not inhibit genera tion of normal cytolytic responses, and neither 'resting' SLE PBMC prior to stimulation nor addition of neutralizing anti-IL 10 mAb or costimulating a nti-CD28 mAb restored generation of SLE cytolytic responses to normal. Neve rtheless, despite the significantly greater cytolytic responses in normal P BMC cultures than in SLE PBMC cultures, cytolytic responses in normal purif ied T cell cultures were only modestly and insignificantly greater than tho se in SLE purified T cell cultures. Moreover, substitution of 'healthy' non -T cells for SLE non-T cells in four of the nine MZ twin-pairs appreciably enhanced cytolytic responses, and substitution of SLE non-T cells for 'heal thy' non-T cells in five of the seven twin-pairs tested appreciably diminis hed cytol) tic responses. Taken together, these results indicate that, in a ddition to any inherent SLE T cell abnormalities, impaired function of SLE non-T cells contributes to impaired generation of nonrestricted CTL activit y.