The regulatory role of transforming growth factor-beta in activation of milk mononuclear cells

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-beta) 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-beta 1 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-beta and extremely high levels of latent TGF-beta. MMCs stimulated with Con A produced higher levels of IL-2 than did the PBMCs of the same animals, and bovine milk TGF-beta and huTGF-beta 1 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-beta is a major immunoregulatory factor in the involuting mammary gland.