title: Study of cord blood natural killer cell suppressor activity.
abstract: We tested the immunosuppressive effect of cord blood (CB) natural killer (NK) cells using highly purified CB NK cells in mixed lymphocyte cultures (MLC) containing autologous CB T cells as responders. Control cultures were done without NK cells. Our findings revealed that CB NK cells induced a dose-dependent inhibition of T lymphocyte proliferation as evidenced by decreased 3H-thymidine incorporation in MLC. The T cell alloproliferation was significantly decreased in the presence of an NK cell to responder cell ratio of 0.1, 0.2 or 0.4 compared with control cultures done without NK cells (p=0.02, 0.003 and 0.0002, respectively). T lymphocyte inhibition was also achieved using irradiated CB NK cells and still demonstrable on addition of disparate CB NK and T cells to the MLC. In agreement with previous reports, adult blood NK cells inhibited the alloreactive T cells in the MLC using adult T lymphocytes as responders. Compared to control cultures done without NK cells, statistically significant inhibition of 3H-thymidine incorporation in MLC was observed at a ratio of NK cells to responder cells ratio of 0.2 or 0.4 (p=0.02). To investigate the mechanism whereby CB NK cells can interfere with the development of alloreactive T cells in MLC, we measured the tumour necrosis factor-alpha (TNF-alpha) concentrations in MLC supernatants using NK cell-depleted or unseparated CB mononuclear cells (MNC) as responders. The results revealed significantly high levels of TNF-alpha in the absence of NK cells (p=0.007). We conclude that CB NK cells suppress alloreactive T lymphocytes as do their counterparts in adult blood. However, the high NK to T cell ratio in CB could contribute to a more marked suppressive potential compared to that in adult blood. The mechanism of NK-mediated inhibition is likely related to disruption of the TNF-alpha pathway of T-lymphocyte activation.
authors.affiliation: Laboratoire de Recherche sur la Biologie de la Moelle Osseuse, Institut Universitaire d'Hématologie EA 1814, Paris VII, France. sanaaelmarsafy@yahoo.com
authors.forename: S
authors.initials: S
authors.lastname: El Marsafy
authors.forename: C
authors.initials: C
authors.lastname: Dosquet
authors.forename: M C
authors.initials: MC
authors.lastname: Coudert
authors.forename: A
authors.initials: A
authors.lastname: Bensussan
authors.forename: E
authors.initials: E
authors.lastname: Carosella
authors.forename: E
authors.initials: E
authors.lastname: Gluckman
mesh_terms: D000328:Adult; D004306:Dose-Response Relationship, Immunologic; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D014409:Tumor Necrosis Factor-alpha