Appearance of Langerhans cells in the epidermis of Tgfb1(-/-) SCID mice: paracrine and autocrine effects of transforming growth factor-beta 1 and -beta 2(1)

• Published in: Journal of investigative dermatology Vol. 117; no. 6; pp. 1574 - 1580
• Main Authors: Thomas, R M, Belsito, D V, Huang, C, Chen Lz, L Z, Ormsby, I, Simmons, W J, Cowin, P, Shaw, J, Doetschman, T, Thorbecke, G J
• Format: Journal Article
• Language: English
• Published: United States 01.12.2001
• Subjects: Animals; Antigen Presentation - immunology; Autocrine Communication - drug effects; Autocrine Communication - immunology; Bone Marrow Transplantation; Epidermis - immunology; Epidermis - pathology; Immunosuppressive Agents - pharmacology; Langerhans Cells - immunology; Langerhans Cells - pathology; Lymph Nodes - immunology; Lymph Nodes - pathology; Mice; Mice, Knockout; Mice, SCID; Paracrine Communication - drug effects; Paracrine Communication - immunology; Spleen - immunology; Spleen - pathology; Tongue - immunology; Tongue - pathology; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - pharmacology; Transforming Growth Factor beta1; Transforming Growth Factor beta2
• ISSN: 0022-202X
• DOI: 10.1046/j.0022-202x.2001.01550.x

A striking immunologic abnormality of normal and SCID Tgfb1(-/-) mice is the total absence of Langerhans cells in their epidermis. Here we show that transfer of Tgfb1(+/-) SCID bone marrow causes, within a few weeks, the appearance of Langerhans cells in the epidermis of gamma-irradiated and unirradiated Tgfb1(-/-) SCID recipients. In addition, local injection of 2 x 10(5) latent transforming growth factor-beta1 cDNA-transduced cloned CD4+ T lymphocytes causes the appearance of Langerhans cells in the ear epidermis of Tgfb1(-/-) SCID mice. This effect is enhanced by antigen-specific activation of these T cells. Injection of recombinant active transforming growth factor-beta 2 into the ear of Tgfb1(-/-) SCID mice also results in the migration of Langerhans cells into the epidermis locally, but no epidermal Langerhans cells are seen after systemic injections of transforming growth factor-beta 2. Our results suggest that transforming growth factor-beta can act in paracrine as well as autocrine fashion to induce the differentiation of precursors into Langerhans cells. Furthermore, these results indicate that the relative roles of different transforming growth factor-beta isoforms in vivo may be influenced by their local availability and/or the regulation of their conversion from latent into active form.