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Arthritis Rheum. 1997 May;40(5):822-33.

Decreased T cell response to anti-CD2 in systemic lupus erythematosus and reversal by anti-CD28: evidence for impaired T cell-accessory cell interaction.

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  • 1University of Southern California School of Medicine, Los Angeles 90033, USA.

Abstract

OBJECTIVE:

To assess the ability of T cells from patients with systemic lupus erythematosus (SLE) to respond to a mitogenic combination of anti-CD2 monoclonal antibodies (MAb), and to learn the molecular basis of the documented defect.

METHODS:

Peripheral blood mononuclear cell (PBMC) populations from individuals with SLE and paired controls were stimulated in vitro with anti-CD2, and the proliferative response was compared with that evoked by stimulation with phytohemagglutinin (PHA) and anti-CD3. Surface markers on lymphocyte populations were assessed by flow cytometry after staining with specific MAb.

RESULTS:

The proliferative response to anti-CD2 was decreased to a greater extent than was the response to anti-CD3 or PHA in SLE patients. This defect was found in approximately one-half of the patients examined, was not associated with disease activity, and was maintained upon repeated testing. Since either monocytes or resting B cells can serve as accessory cells for T cells following activation by anti-CD2, we examined the T cell response after depletion of adherent cells. In approximately two-thirds of the individuals with a decreased response, depletion of monocytes or substitution of monocytes with allogeneic, resting B cells from normal donors corrected the defect. The addition to PBMC of anti-CD28, but not of a neutralizing antibody to interleukin-10, largely reversed the anti-CD2 proliferative defect. Significantly fewer CD8+ T cells expressed CD28 in SLE, and this defect was also documented, to a lesser extent, in CD4+ cells.

CONCLUSION:

This study provides evidence that some functional T cell defects in SLE may be due, at least in part, to decreased CD28-mediated costimulatory activity following the interaction of T cells with conventional accessory cells.

PMID:
9153542
[PubMed - indexed for MEDLINE]
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