Requirement of the IL-2 Receptor β Chain for the Development of Vγ3 Dendritic Epidermal T Cells

Abstract

Vgamma3 TCR cells develop in the fetal thymus and migrate to the skin as dendritic epidermal T cells (DETC). Fetal Vgamma3 thymocytes differentiate from immature heat stable antigen (HSA)high cells to mature HSAlow cells and the latter subset predominantly expresses IL-2 receptor beta chain (IL-2Rbeta). In this study, the role of IL-2Rbeta in the development of Vgamma3 cells was determined in IL-2Rbeta-deficient mice. There was a moderate reduction of mature HSAlow Vgamma3 thymocytes in IL-2Rbeta-deficient mice. Small numbers of Vgamma3 DETC were detected in the fetal skin of IL-2Rbeta-deficient mice, but they were absent in newborn and adult mice. These results suggest that IL-2Rbeta may transduce the crucial signal for survival and/or expansion of Vgama3 cells in the fetal thymus and in the fetal skin. In normal mice, IL-15 but not IL-2 mRNA was expressed in the fetal epidermis and exogenous addition of low concentration of IL-15 to fetal skin organ culture induced proliferation of Vgamma3 DETC. The dependence of fetal Vgamma3 DETC on the expression of IL-2Rbeta and the presence of IL-15 mRNA in the fetal epidermis imply an essential role of IL-15 signaling through IL-2Rbeta in the selective localization of this gammadelta T cell subpopulation in the skin.

Enforced Expression of Bcl-2 Partially Restores Cell Numbers but Not Functions of TCRγδ Intestinal Intraepithelial T Lymphocytes in IL-15-Deficient Mice

“…However, recent studies showed that enforced expression of Bcl-2 did not restore TCR␥␦ IEL in the skin of not only IL-2/15R␤ KO mice but also V␥5/V␦1 TCR-transgenic IL-2/15R␤ KO mice (44), suggesting that TCR␥␦ s-IEL most likely receive proliferation and survival signals from IL-15 independently of Bcl-2. In support of this, it was shown that exogenous addition of IL-15 to organ culture of fetal skin induced proliferation of V␥5 s-IEL (45). Similar to the case with TCR␥␦ s-IEL, enforced expression of Bcl-2 did not restore the number of NKT cells in IL-15 KO mice.…”

Enforced Expression of Bcl-2 Restores the Number of NK Cells, But Does Not Rescue the Impaired Development of NKT Cells or Intraepithelial Lymphocytes, in IL-2/IL-15 Receptor β-Chain-Deficient Mice

“…Liver lymphocytes, intestinal IEL, and epidermal cells were prepared as described previously (27,70,71). …”

“…Diluted cDNA was amplified by PCR using primers specific for TCR V␣14-J␣281 (74). The amount of template cDNA was normalized using primers for ␤-actin (27).…”

“…RNA extraction and reverse transcription using pd(N) 6 primers were performed as described (27). Diluted cDNA was amplified by PCR using primers specific for TCR V␣14-J␣281 (74).…”

“…However, NK cells and TCR␣␤ intestinal IEL develop almost normally in these mice (18,(21)(22)(23). In contrast, mice deficient for the shared ␤-chain of IL-2R and IL-15R (IL-2/IL-15R␤ Ϫ/Ϫ mice) display normal development of conventional ␣␤ T cells and B cells but have dramatically reduced numbers of NK cells, TCR␥␦ and TCR␣␤CD8␣␣ subsets of intestinal IEL, and NK1.1 ϩ TCR␣␤ ϩ NKT cells, and no skin IEL (23)(24)(25)(26)(27). Because IFN regulatory factor-1 Ϫ/Ϫ mice (in which the IL-15 gene expression is impaired (28,29)), IL-15 Ϫ/Ϫ mice, and IL-15R␣ Ϫ/Ϫ mice are similarly deficient in NK cells, NKT cells, and CD8␣␣ intestinal IEL (28 -31), and because IL-15 Ϫ/Ϫ mice have no skin IEL (32), the development of these innate lymphocytes may depend primarily on IL-15/IL-15R rather than IL-2/IL-2R.…”