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).
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.
Thomas
R M
RM
Department of Pathology, New York University School of Medicine, New York, New York 10016, USA.
Belsito
D V
DV
Huang
C
C
Chen Lz
L Z
LZ
Ormsby
I
I
Simmons
W J
WJ
Cowin
P
P
Shaw
J
J
Doetschman
T
T
Thorbecke
G J
GJ
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D019898:Autocrine Communication / Q000187:drug effects / Q000276:immunology; D016026:Bone Marrow Transplantation; D004817:Epidermis / Q000276:immunology / Q000473:pathology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007801:Langerhans Cells / Q000276:immunology / Q000473:pathology*; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D019899:Paracrine Communication / Q000187:drug effects / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D014059:Tongue / Q000276:immunology / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2
D007166:Immunosuppressive Agents; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2