IL-7 OVEREXPRESSION IN TRANSGENIC MOUSE KERATINOCYTES CAUSES A LYMPHOPROLIFERATIVE SKIN-DISEASE DOMINATED BY INTERMEDIATE TCR CELLS - EVIDENCE FOR A HIERARCHY IN IL-7 RESPONSIVENESS AMONG CUTANEOUS T-CELLS

IL-7 is a keratinocyte-derived lymphocyte growth factor critical for t he development of gamma delta T cells including murine dendritic epide rmal T cells (DETC). We derived transgenic mice that overexpress IL-7 in basal keratinocytes under the control of the human K14 promoter. Th ese K14/IL-7 mice develop dermal and epidermal T cell infiltrates asso ciated with alopecia. This lymphoproliferative skin disease is substan tially more severe in mice homozygous for the K14/IL-7 transgene. Conv entional DETC expressing a V gamma 5V delta 1 TCR are rare or absent a mong the cutaneous T cells in these mice. The T cells in the skin infi ltrates of young K14/IL-7 mice are predominantly gamma delta T cells t hat express intermediate levels of TCR, are negative for E-cadherin, o ften lack expression of CD2, and include cells that coexpress NK1.1. T cells expressing intermediate levels of a TCR-alpha beta are also pre sent in transgenic skin, and progressively increase in number as the m ice age. Phenotypically similar intermediate gamma delta and alpha bet a T cell subsets also constitute the major lymphocyte populations reco vered from organ culture of normal mouse skin in the presence of IL-7, suggesting that the T cells that accumulate in the epidermis of K14/I L-7 mice are derived from precursors normally resident in skin. We con clude that intermediate TCR cells, some of which coexpress NK1.1, can be selectively expanded in skin under the influence of IL-7 produced l ocally. Our results also suggest that features of the epidermal microe nvironment besides keratinocyte-derived IL-7 account for the normal pr edominance of V gamma 5V delta 1 DETC in mouse epidermis.