J. Exp. Med.
Volume 184 December 1996 2417-2422

BRIEF DEFINITIVE REPORT:
A Role for Endogenous Transforming Growth Factor 1 in Langerhans Cell Biology:  The Skin of   Transforming Growth Factor 1 Null Mice Is Devoid of  Epidermal Langerhans Cells

By Teresa A. Borkowski,^* John J. Letterio, Andrew G. Farr,^§ and Mark C. Udey^*

From the ^* Dermatology Branch and  the Laboratory of Chemoprevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1908; and the ^§ Department of Biological Structure, University of Washington, Seattle, Washington 98195

Transforming growth factor 1 (TGF-1) regulates leukocytes and epithelial cells. To determine whether the pleiotropic effects of TGF-1, a cytokine that is produced by both keratinocytes and Langerhans cells (LC), extend to epidermal leukocytes, we characterized LC (the epidermal contingent of the dendritic cell [DC] lineage) and dendritic epidermal T cells (DETC) in TGF-1 null (TGF-1 /) mice. I-A⁺ LC were not detected in epidermal cell suspensions or epidermal sheets prepared from TGF-1 / mice, and epidermal cell suspensions were devoid of allostimulatory activity. In contrast, TCR-⁺ DETC were normal in number and appearance in TGF-1 / mice and, importantly, DETC represented the only leukocytes in the epidermis. Immunolocalization studies revealed CD11c⁺ DC in lymph nodes from TGF-1 / mice, although gp40⁺ DC were absent. Treatment of TGF-1 / mice with rapamycin abrogated the characteristic inflammatory wasting syndrome and prolonged survival indefinitely, but did not result in population of the epidermis with LC. Thus, the LC abnormality in TGF-1 / mice is not a consequence of inflammation in skin or other organs, and LC development is not simply delayed in these animals. We conclude that endogenous TGF-1 is essential for normal murine LC development or epidermal localization.

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