Differential Roles of Cytokine Receptors in the Development of Epidermal T Cells

* IL-7 and IL-15 play important roles in ␥␦ T cell development. These receptors transmit proliferation and/or survival signals in ␥␦ T cells. In addition, the IL-7R promotes recombination and transcription in the TCR ␥ locus. To clarify the role of the cytokine receptors in the development of epidermal ␥␦ T cells, we introduced a V␥3/V␦1 TCR transgene, derived from Thy-1 ؉ dendritic epidermal T cells (DETC), into IL-7R␣-deficient mice, and we found that they partly rescued ␥␦ T cells in the adult thymus but not in the spleen. Introduction of an additional Bcl-2 transgene had a minimal effect on ␥␦ T cells in the adult thymus of these mice. In contrast to the adult thymus, the introduction of the V␥3/V␦1 TCR transgene into IL-7R␣ ؊/؊ mice completely restored V␥3 ؉ T cells in the fetal thymus and DETC in the adult skin. On the contrary, the same V␥3/V␦1 TCR transgene failed to rescue DETC in the skin of IL-2R␤-deficient mice, even with the additional Bcl-2 transgene. These results suggest that the IL-2/IL-15R, rather than the IL-7R, plays an essential role in proliferation and survival of DETC in the fetal thymus and the skin. In contrast, the IL-7R is probably essential in the induction of V-J recombination of TCR␥ genes. Thus, this study proves that IL-7R and IL-2/IL-15R serve differential functions in epidermal ␥␦ T cell development. D evelopment of ␥␦ T cells has unique features in contrast to ␣␤ T cell development (1–3). ␥␦ T cells expressing a specific V ␥-chain appear as several successive waves in the developing thymus, and each of them shows distinct tissue distribution in the adult mouse. V␥3 ϩ T cells develop as the first wave in the fetal thymus and become Thy-1 ϩ dendritic epidermal T cells (DETC) 4 in the adult skin. V␥4 ϩ T cells are the second wave and are distributed in the epithelium of the lung, tongue, and vagina. These two epithelial T cell subsets express homogeneous ␥␦ TCRs, V␥3/V␦1 or V␥4/V␦1, with a single species of V␥-J␥ junctional sequence. V␥2 ϩ T cells develop in the thymus after these cells and reside mainly in the spleen and the lymph nodes. In contrast, the majority of ␥␦ intestinal intraepithelial lymphocytes (IEL) express V␥5 TCR and develop in the gut from cryptopatches (4, 5). This sequential development of ␥␦ T cells is regulated by the V-J recombination of the TCR␥ …