Differential roles of cytokine receptors in the development of epidermal gamma delta 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.
Ye
S K
SK
Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Maki
K
K
Lee
H C
HC
Ito
A
A
Kawai
K
K
Suzuki
H
H
Mak
T W
TW
Chien
Y
Y
Honjo
T
T
Ikuta
K
K
D000375:Aging / Q000235:genetics / Q000276:immunology; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism*; D005333:Fetus / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics; D018121:Receptors, Cytokine / Q000502:physiology*; D020395:Receptors, Interleukin-7 / Q000172:deficiency / Q000235:genetics; D012867:Skin / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019076:Transgenes / Q000276:immunology
D016692:Receptors, Antigen, T-Cell, gamma-delta; D018121:Receptors, Cytokine; D020395:Receptors, Interleukin-7