The Regulatory Role of Transforming Growth Factor-Beta in Activation of Milk Mononuclear Cells


Department of Pathobiology, U-89, University of Connecticut, Storrs, CT 06269-3089.


PROBLEM: Immunoregulatory role of milk mononuclear cells and cytokines during the involution of the mammary gland.

METHOD OF STUDY: Bioassays were used to determine the levels of transforming growth factor beta (TGF-β) and interleukin-2 (IL-2) and their effects on milk mononuclear cells (MMCs). RESULTS: MMCs collected from involuting glands were less responsive to Con A stimulation than peripheral blood mononuclear cells (PBMCs), and purified huTGF-β1 inhibited the activation of both MMCs and PBMCs by Con A. Furthermore, secretions collected over a period of approximately 4 weeks into the involution period contained high levels of active TGF-β and extremely high levels of latent TGF-β. MMCs stimulated with Con A produced higher levels of IL-2 than did the PBMCs of the same animals, and bovine milk TGF-β and huTGF-β1 significantly inhibited the IL-2 production by MMCs. Mammary secretions of involuting glands did not contain any detectable levels of IL-2, and they inhibited the growth of the IL-2-dependent bovine lymphoblastoid T cell line (BLTC), even in the presence of 10 U/ml of rBo IL-2.

CONCLUSIONS: The findings suggest that TGF-β is a major immunoregulatory factor in the involuting mammary gland.