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Division of Rheumatology and Immunology, Department of Medicine, University of Southern California School of Medicine, Los Angeles, CA 90033
Although the phenomenon of immunosuppression is well established, the mechanisms involved in the generation of lymphocytes with down-regulatory activity are poorly understood. Unlike anti-CD3 antibodies, mitogenic combinations of anti-CD2 antibodies do not stimulate human PBL to produce IgM or IgG. In determining the reason for this difference, we have found that anti-CD2 triggers an inhibitory circuit facilitated by TGF-ß provided by NK cells. Stimulation of PBL with anti-CD2, but not anti-CD3, generated substantial amounts of active TGF-ß. NK cells were found to be a significant source of TGF-ß and were the only lymphocyte population that constitutively produced this cytokine. Anti-CD2 enhanced the production of active TGF-ß by purified NK cells. TGF-ß. After the removal of NK cells or the addition of anti-TGF-ß, anti-CD2 could stimulate Ig production. Anti-TGF-ß had to be added within the first 24 h for a maximal effect. Moreover, a short, overnight exposure of CD8+ T cells to TGF-ß could prime them for suppressor activity provided that IL-2 was also present. Thus, the presence of active TGF-ß coincident with CD8+ T cell activation can condition these cells to mediate down-regulatory activity, and NK cells can serve as the source of this cytokine.
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