Comparison of the immunosuppressive properties of milk growth factor and transforming growth factors beta 1 and beta 2


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Comparison of the immunosuppressive properties of milk growth factor and transforming growth factors beta 1 and beta 2
Journal of Immunology
Stoeck  M., Ruegg  C., Miescher  S., Carrel  S., Cox  D., Von Fliedner  V., Alkan  S.
0022-1767 (Print)
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Research Support, Non-U.S. Gov't --- Old month value: Nov 15
The effects of the newly isolated bovine milk growth factor (MGF) which shows N-terminal homology to transforming growth factor beta 2 were compared with the effects of porcine transforming growth factor beta 1 and beta 2 (pTGF-beta 1 and -beta 2) on human T lymphocyte activation. Freshly isolated human PBMC were stimulated with either PHA, anti-CD3 + phorbol-12,13-dibutyrate (PDBu), or with a combination of ionomycin + PDBu. MGF, pTGF-beta 1, and pTGF-beta 2 decreased mitogen-induced [3H]thymidine incorporation by 30 to 75% in a dose-dependent manner. The maximum degree of inhibition was obtained at 1 ng/ml (40 pM) and could not be increased by increasing the concentration of teh transforming growth factor 10-fold. Stimulation of fresh T cells with the recall Ag tetanus toxoid was also inhibited (85%) by MGF at pM concentrations as was the proliferation of a human T cell clone specific for purified protein derivative. The effects of MGF and pTGF-beta 1 on anti-CD3-mediated increase of intracellular Ca2+ (Cai2+) was investigated by using the Fura-2 method. Neither MGF nor pTGF-beta 1 inhibited this increase in Cai2+ induced by a mitogenic concentration of anti-CD3 antibody. In order to determine whether TGF-beta preferentially inhibited the CD4+ or CD8+ subpopulation of human T cells, a limiting dilution analysis system, which allows every T cell to proliferate, was used. pTGF-beta 1 at a concentration of 5 ng/ml decreased the frequency of proliferating T cell precursors of both the CD4+ and CD8+ subsets to a similar extent. Furthermore, MGF, pTGF-beta 1, and pTGF-beta 2 also decreased IL-2 mediated [3H]thymidine incorporation into human PBL Con A blasts and the IL-4-mediated [3H]thymidine incorporation of purified T lymphocytes costimulated with PDBu by 70%. In conclusion, bovine MGF exerts suppressive effects on human T cells stimulated with Ag, mitogens, or interleukins, and the degree of T cell suppression is similar (or identical) to those of pTGF-beta 1 or -beta 2.
Animals Antigens, CD3 Antigens, Differentiation, T-Lymphocyte/immunology Calcium/metabolism Cattle Growth Substances/*immunology Humans Interleukin-2/pharmacology Interleukin-4/pharmacology Leukocyte Count Lymphocyte Activation Lymphocytes/immunology/metabolism Milk Proteins/*immunology Phenotype Receptors, Antigen, T-Cell/immunology Stem Cells/immunology Suppressor Factors, Immunologic/*physiology Swine T-Lymphocytes/immunology Thymidine/metabolism Transforming Growth Factors/*immunology
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28/01/2008 8:36
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