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

Division of Rheumatology, Department of Medicine, Los Angeles County and University of Southern California Medical Center and University of Southern California School of Medicine, Los Angeles, California 90033, USA; Division of Rheumatology and Immunology, University of Southern California, 2011 Zonal Ave. HMR 711, Los Angeles, CA 90033, USA.

A S Hamilton

D M Deapen

T M Mack

Department of Preventive Medicine, University of Southern California School of Medicine, Los Angeles, California 90033, USA

D A Horwitz

Division of Rheumatology, Department of Medicine, Los Angeles County and University of Southern California Medical Center and University of Southern California School of Medicine, Los Angeles, California 90033, USA

To determine whether non-T cells contribute to impaired generation of nonrestricted cytotoxic T lymphocyte (CTL) activity in human SLE, peripheral blood mononuclear cells (PBMC) and sorturified T cells from normal subjects and SLE patients were stimulated with anti-CD3 mAb, maintained in IL2, and assayed for cytolytic activity against 51Cr-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 responses were significantly lower in SLE PBMC cultures than in normal PBMC cultures. Addition of SLE serum to normal PBMC cultures did not inhibit generation of normal cytolytic responses, and neither `resting' SLE PBMC prior to stimulation nor addition of neutralizing anti-IL10 mAb or costimulating anti-CD28 mAb restored generation of SLE cytolytic responses to normal. Nevertheless, despite the significantly greater cytolytic responses in normal PBMC cultures than in SLE PBMC cultures, cytolytic responses in normal purified T cell cultures were only modestly and insignificantly greater than those 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 `healthy' non-T cells in five of the seven twin-pairs tested appreciably diminished cytolytic responses. Taken together, these results indicate that, in addition to any inherent SLE T cell abnormalities, impaired function of SLE non-T cells contributes to impaired generation of nonrestricted CTL activity.

Key Words: cytotoxicity • systemic lupus erythematosus • T cells • non-T cells

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