Dysregulated expression of the IL-2 receptor beta-chain abrogates development of NK cells and Thy-1+ dendritic epidermal cells in transgenic mice.
The IL-2 receptor beta-chain (IL-2R beta), a specificity-determining subunit in the IL-2R complex with a restricted tissue distribution pattern, is essential for signal transduction. Our previous studies demonstrate that the continuous treatment of mice with anti-IL-2R beta resulted in the complete disappearance of NK cells and Thy-1+ dendritic epidermal cells (Thy-1+ dEC), suggesting that signals through IL-2R beta are critically involved in development of these lymphocyte subsets. However, these lymphocyte subsets are reported to be apparently unaffected in the IL-2-deficient mice. To further examine the biological roles of the IL-2R beta, transgenic mice carrying the IL-2R beta transgene were generated. In these mice, high levels of the cell surface expression of the IL-2R beta were observed in essentially all hematopoietic lineage cells, and CD4+ T cells as well as CD8+ T cells showed vigorous cell proliferation upon IL-2 stimulation. Surprisingly, NK cells marked with a high expression of NK1.1 in the spleen and Thy-1+ dEC in the skin were completely absent in transgenic mice. However, the development of other lymphocyte subsets including conventional alpha beta TCR+ cells, gamma delta TCR+ cells and B cells remained apparently intact. From these observations together with previous data on IL-2-deficient mice, we speculate that factors, other than IL-2 that utilizes the IL-2R beta as its functional receptor subunit, may have a vital role in the development of NK cells and Thy-1+ dEC. Implications for possible in vivo functions of over-expressed IL-2R beta are discussed.
D000818:Animals; D001483:Base Sequence; D003713:Dendritic Cells / Q000502:physiology*; D000078404:Epidermal Cells; D005260:Female; D007694:Killer Cells, Natural / Q000502:physiology*; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000502:physiology*; D018800:Thy-1 Antigens / Q000032:analysis*
D015375:Receptors, Interleukin-2; D018800:Thy-1 Antigens