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Generation of an inhibitory circuit involving CD8+ T cells, IL-2, and NK cell-derived TGF-beta: contrasting effects of anti-CD2 and anti-CD3.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 1998 Mar 01; Vol. 160 (5), pp. 2248-54. - Publication Year :
- 1998
-
Abstract
- 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-beta provided by NK cells. Stimulation of PBL with anti-CD2, but not anti-CD3, generated substantial amounts of active TGF-beta. NK cells were found to be a significant source of TGF-beta and were the only lymphocyte population that constitutively produced this cytokine. Anti-CD2 enhanced the production of active TGF-beta by purified NK cells. TGF-beta. After the removal of NK cells or the addition of anti-TGF-beta, anti-CD2 could stimulate Ig production. Anti-TGF-beta had to be added within the first 24 h for a maximal effect. Moreover, a short, overnight exposure of CD8+ T cells to TGF-beta could prime them for suppressor activity provided that IL-2 was also present. Thus, the presence of active TGF-beta 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.
- Subjects :
- Adult
Animals
Cell Line
Cells, Cultured
Cytotoxicity, Immunologic
Humans
Immunoglobulin G biosynthesis
Immunoglobulin M biosynthesis
Killer Cells, Natural metabolism
Lymphocyte Activation
Mink
Transforming Growth Factor beta immunology
Antibodies, Monoclonal pharmacology
CD2 Antigens immunology
CD3 Complex immunology
CD8-Positive T-Lymphocytes immunology
Down-Regulation immunology
Interleukin-2 physiology
Killer Cells, Natural immunology
Transforming Growth Factor beta physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 160
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 9498764