Interleukin 7 receptor engagement stimulates tyrosine phosphorylation, inositol phospholipid turnover, proliferation, and selective differentiation to the CD4 lineage by human fetal thymocytes.

Abstract

The purposes of this study were to elucidate the effects of recombinant human interleukin 7 (rhIL-7) on proliferation as well as differentiation of human fetal thymocytes and to analyze the biochemical nature ofthe IL-7 receptorlinked transmembrane signal. In the absence of costimulants, rhIL-7 stimulated the in vitro proliferation and colony formation of CD4+CD8' double-positive immature fetal thymocytes. Furthermore, rhIL-7 promoted partial differentiation of immature thymocytes with a selective advantage for the development of CD4+CD8-single-positive thymocytes. Our observations suggest that IL-7 likely has an important regulatory role during the earliest stages of human T-cell ontogeny. Stimulation of fetal thymocytes with rhIL-7 resulted in enhance tyrosine phosphorylation of three distinct phosphoproteins with molecular masses of 72, 98, 123, and 190 kDa and induced a rapid and biphasic increase in the production of inositol 1,4,5-trisphosphate, which was inhibitable by the tyrosine protein kinase inhibitor genistein. Thus, the transmembrane signal triggered by engagement of the IL-7 receptor is intimately linked to a functional tyrosine protein kinase pathway and stimulates the inositol phospholipid turnover and proliferation, as well as selective differentiation to the CD4 lineage, by human fetal thymocytes.

Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia

“…Although we chose IL-7 because of its ability to simultaneously stimulate thymopoiesis, 14,43 increase T-cell proliferation, 44,45 and prolong survival of mature T cells, 46 it was not clear before this study which if any of these functions of IL-7 would be effective in T-cell recovery in ICL. ICL T cells express high levels of activation and proliferation markers 3 and, as recently reported, are prematurely senescent.…”

Critical cytoplasmic region of the interleukin 6 signal transducer gp130 is conserved in the cytokine receptor family.

“…It would be of interest were the homologous part to play a role in the interaction of tyrosine kinases. Several cytokines, such as IL-2, IL-3, and IL-7, have been reported to induce tyrosinephosphorylation of cellular proteins and activation of tyrosine kinases (30)(31)(32). In contrast, the growth factor receptors such as epidermal growth factor receptor, colony-stimulating factor 1 receptor, and platelet-derived growth factor receptor, which possess the tyrosine kinase domain in the cytoplasmic region, do not contain box 1-and box 2-like seProc.…”

“…Some cytokines, such as IL-2, IL-3, and IL-7, phosphorylate tyrosine in cellular proteins, including the receptor (30)(31)(32). We examined whether gp130 was tyrosine-phosphorylated in response to IL-6.…”

Serum levels of IL-7 in bone marrow transplant recipients: relationship to clinical characteristics and lymphocyte count

“…IL-7 was originally identified by its ability to induce proliferation of B cell progenitors in vitro and in vivo and was subsequently shown to stimulate T lymphopoiesis. [17][18][19][20][21][22][23][24][25][26] Recently, we have shown that administration of IL-7 significantly enhances immune recovery in mice after T celldepleted BMT. 27 Therefore, production of IL-7 may be one of the mechanisms regulating de novo production of T lymphocytes after BMT.…”