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

IL-7 and IL-15 play important roles in gammadelta T cell development. These receptors transmit proliferation and/or survival signals in gammadelta T cells. In addition, the IL-7R promotes recombination and transcription in the TCR gamma locus. To clarify the role of the cytokine receptors in the development of epidermal gammadelta T cells, we introduced a Vgamma3/Vdelta1 TCR transgene, derived from Thy-1+ dendritic epidermal T cells (DETC), into IL-7Ralpha-deficient mice, and we found that they partly rescued gammadelta T cells in the adult thymus but not in the spleen. Introduction of an additional Bcl-2 transgene had a minimal effect on gammadelta T cells in the adult thymus of these mice. In contrast to the adult thymus, the introduction of the Vgamma3/Vdelta1 TCR transgene into IL-7Ralpha-/- mice completely restored Vgamma3+ T cells in the fetal thymus and DETC in the adult skin. On the contrary, the same Vgamma3/Vdelta1 TCR transgene failed to rescue DETC in the skin of IL-2Rbeta-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 TCRgamma genes. Thus, this study proves that IL-7R and IL-2/IL-15R serve differential functions in epidermal gammadelta T cell development.