Characteristics of anti-T-cell antibodies in systemic lupus erythematosus: Evidence for selective reactivity with normal suppressor cells defined by monoclonal antibodies

Abstract

Monoclonal antibodies have been produced to multiple human T-cell surface antigens. While some of these antibodies define antigens represented on all peripheral T cells (T3), others are restricted in their reactivity to the human inducer T-cell subset (T4) or reciprocal cytotoxic/suppressor subset (T5/T8). In the present study, the relationship of naturally occurring anti-T-cell antibodies found in patients with systemic lupus erythematosus (SLE) to these T-cell subsets was examined. T cells were purified by Sephadex G-200 anti-F(ab′) 2 affinity chromatography and E rosetting techniques and subsequently, inducer or suppressor subsets eliminated with T4 or T8 and rabbit complement. Utilizing indirect immunofluorescence on the Fluorescence Activated Cell Sorter (FACS), it was found that the anti-T-cell antibodies from 10 patients with active systemic lupus erythematosus (SLE) reacted with approximately 80% of the suppressor-enriched (T4 −)subset. In contrast, they were virtually unreactive with inducer-enriched (T8 −)subset. In reciprocal studies, anti-T-cell antibody-reactive T cells (SLE +) were eliminated with SLE sera and the residual T cells reacted with monoclonal antibodies on the FACS. These studies showed that the T4 + inducer population was increased after elimination of the SLE + T-cell subset whereas the T5 + suppressor population was diminished. Moreover, in functional studies, it was shown that when the SLE + T-cell subset was removed, there was significant enhancement of pokeweed mitogen (PWM)-driven immunoglobulin synthesis by autologous normal B lymphocytes. In addition, lysis of this same SLE + subset resulted in an increase in native DNA-driven Ig synthesis by B lymphocytes from patients with inactive SLE. These studies demonstrate that the anti-T-cell antibodies found in patients with active SLE are selectively reactive with the human suppressor T-cell population as defined by monoclonal antibodies.