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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Highly enriched pluripotent and multipotent hematopoietic stem cells (HSCs) are isolated from bone marrow and fetal liver as Thy-1loLin-Sca-1+ cells. Pluripotent HSCs express c-kit receptor on their surface, but the generation and proliferation of early fetal HSCs take place in the absence of steel factor. T precursor cells migrate into the fetal thymus by chemotactic mechanism. CD4lo precursors represent a newly defined phase of T-cell development in the thymus between the bone marrow-derived stem cells and the CD4-8- intrathymic precursors. Only fetal, but not adult, HSCs have the capacity to differentiate into V gamma 3+ and V gamma 4+ T cells under the fetal thymic microenvironment, and HSC themselves may lose some of their developmental potential during ontogeny. It is postulated that HSCs are the locus of a complicated but precise developmental clock that may determine both the time-dependent closure of some gene loci (e.g. V gamma 3 and V gamma 4 T cell receptor, and embryonic and fetal globin) and the activation of others (e.g. the N nucleotide insertion machinery).
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PMID:Lymphocyte development from stem cells. 137 74

Ten percent of 15-day fetal thymocytes of mice were Pgp-1+Thy-1lo cells. Half were strongly stained with monoclonal antibodies (mAb) recognizing the oncogene product, c-kit, but were not stained with mAb against non-T cell markers such as B220, Mac-1 and Gr-1. The isolated Pgp-1+c-kit+ thymocytes showed no rearranged bands for V-DJ and D-J of T cell receptor (TcR) beta, but Pgp-1(-)-c-kit- thymocytes showed D-J rearranged bands. Both cells expressed the RAG-2 gene which is required for the V(D)J recombination process. When Pgp-1+c-kit+ thymocytes were cultured in 2-deoxyguanosine-treated alymphocytic fetal thymus, they became TcR-expressing mature type T cells, but this differentiation was reduced by the addition of anti c-kit mAb. These data indicate that Pgp-1+c-kit+ thymocytes are pro-T cells with the potential to differentiate mature T cells in the thymic environment. This study also indicates that c-kit-mediated signals promote the differentiation of thymocytes during their early stages.
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PMID:Pro-T cells in fetal thymus express c-kit and RAG-2 but do not rearrange the gene encoding the T cell receptor beta chain. 751 11

Ten cell lines recently established from paediatric patients with acute lymphoblastic leukaemia (ALL) were examined for expression of P145c-kit, the growth factor receptor encoded by the c-kit proto-oncogene, by immunofluorescence and flow cytometry using monoclonal antibody YB5.B8. Three of five T-ALL cell lines, but none of five B lineage ALL cell lines displayed significant binding of the antibody. The cell line with the highest level of binding was PER-423 (Kees et al, Leukemia Res 1993; 17: 51-59 which has the phenotype CD7+, CD56bright, CD2-, CD4-, CD5-, CD8-, CD16-, has rearranged T cell receptor beta-chain genes, expresses cytoplasmic CD3 and is strictly dependent on interleukin 2 (IL-2) for proliferation. Recombinant to act in synergy with IL-2 to promote proliferation of PER-423 cells. In five experiments, SLF increased the maximal amount of proliferation by 105 +/- 15%, and decreased the level of IL-2 required for a half-maximal response by 43 +/- 7%. The cells constitutively express the intermediate affinity IL-2 receptor (beta/gamma), but can be induced in the presence of phorbol ester to express the alpha chain (CD25, Tac) which confers high affinity binding of IL-2. In contrast, the alpha chain was not induced by SLF. The enhancement of proliferation of PER-423 cells by SLF could be prevented by inclusion in the assay of a blocking monoclonal antibody to P145c-kit. These experiments demonstrate that SLF/P145c-kit can provide a significant growth stimulus for ALL cells, and PER-423 cells may be a useful system for investigating the mechanism of synergy between SLF and IL-2.
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PMID:Synergistic action of interleukin-2 and Steel factor (SLF) on a human T lymphoblastoid cell line. 754 Oct 97

CD34, a stem cell marker, has been shown to be expressed on human CD3-CD4-CD8- (triple-negative; TN) thymocytes. Phenotypic and functional analyses suggest the following differentiation sequence: CD34+1-3-4-8(-)--> CD34+1+3-4 +/- 8(-)-->CD34-1+3-4+8(+/-)-->CD34-1++3-4+8+. In this report, we examined cytokine receptor gene expression on these subsets by reverse transcription-polymerase chain reaction analysis (RT-PCR). We were able to detect interleukin-7 receptor (IL-7R), c-kit and IL-2R gamma in all CD34+ thymocyte subsets, consistent with previous functional studies. We found IL-1R, granulocyte/macrophage colony-stimulating factor receptor-alpha and IL-4R transcripts in CD3- and CD34+ subsets. Secondly, we investigated T cell receptor (TCR)-delta and -beta gene rearrangement and transcription in CD34+ thymocytes. Our results show that a full-length TCR-delta transcript and the recombination activating genes RAG-1 and RAG-2 mRNA were already expressed in the CD34+1- subset. Mature V beta-containing TCR transcripts were also detected in the CD34+1+ subset, but not in the CD1- fraction. Furthermore, PCR analysis of D-J beta gene rearrangements showed that > or = 70% of CD34+1- cells are in a TCR beta germ-line configuration, although D-J beta recombination had already started in this population.
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PMID:CD34-positive early human thymocytes: T cell receptor and cytokine receptor gene expression. 758 13

Pluripotent lymphohematopoietic stem cells are probably confined to bone marrow cells expressing CD34 surface molecules. To investigate the capacity of adult human CD34+ bone marrow cells to differentiate along the T lymphoid lineage, we plated purified CD34+ cells from healthy adults in liquid culture on adherent thymic stromal cells prepared from HLA- or blood group-mismatched postnatal thymic tissue. We show that purified CD34+CD3-CD4-CD8- bone marrow cells contained progenitors with the ability to differentiate into CD4+ and CD8+ T lymphocytes expressing surface (s)CD3 and T cell receptor alpha/beta in vitro. These progenitors were found in the CD34+CD2+sCD3-CD4-CD8-, CD34+CD7+sCD3-CD4-CD8-, and CD34+CD2+CD7+sCD3-CD4-CD8-, as well as in the CD34+CD2-sCD3-CD4-CD8-, CD34+CD7-sCD3-CD4-CD8-, and CD34+CD2-CD7-sCD3-CD4-CD8- subsets, indicating that T lymphocyte progenitors sensitive to signals mediated by thymic stroma in vitro are not restricted to CD34+ cells already coexpressing early T lymphocyte-associated markers. Finally, we show that T lymphopoiesis was enhanced by c-kit ligand.
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PMID:T lymphocyte differentiation in vitro from adult human prethymic CD34+ bone marrow cells. 768 29

Murine embryonic stem (ES) cells represent a model system for studying certain aspects of hemopoiesis because they can differentiate in vitro into several cell types, including those of the hemopoietic system. We developed cell culture conditions in which ES cells undergo hemopoietic differentiation in a low-oxygen (5% O2) atmosphere without additional exogenous factors. After 15-20 days of culture under these conditions, cells bearing surface markers found on cells of the lymphoid lineage (Thy1+, Pgp-1+, c-kit+ and B-220+) were detected. After 13-15 days, transcripts for the recombinase activating genes (RAG) 1 and 2, interleukin (IL) 7, IL-7 receptor and c-kit were expressed. We also investigated rearrangements of the immunoglobulin (Ig) heavy and light chain and the T cell receptor (TCR) loci. After 15 days of differentiation, we detected DJH gene rearrangement with N-region diversity. Productive VHDJH rearrangements are found after 20 days, paralleled by V Kappa J Kappa recombinations indicating a developmental stage comparable, at least, with that of pre B cells. Rearrangements of TCR gamma as well as delta chain segments were also observed, but no TCR beta chain rearrangement. These results demonstrate that ES cells reproducibly generate lymphoid cells in vitro.
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PMID:In vitro generation of lymphoid precursors from embryonic stem cells. 795 93

Growth factors have been implicated in thymocyte development, but mutants lacking cytokines, or their receptors, have failed to reveal essential roles for growth/differentiation factors in the thymus. Mutations in the receptor tyrosine kinase c-kit and the common cytokine receptor gamma chain (gamma c) reduce cellularity, but are permissive for thymocyte development. We now report that thymocyte development is completely abrogated in mice lacking both c-kit and gamma c (c-kit-gamma c-). Thymic hypocellularity is so severe that the T cell receptor repertoire fails to form except for monoclonal or oligoclonal beta chain DJ rearrangements. B lymphopoiesis is only mildly reduced in c-kit-gamma c- as compared with c-kit+gamma c- mice, and hematological values are identical comparing c-kit-deficient and c-kit-gamma c- mice. These experiments reveal essential, overlapping, and synergistic functions for two distinct signaling pathways, one utilizing c-kit and the other cytokine receptor gamma c complexes coupling to Janus kinases and signal transducers and activators of transcription.
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PMID:Pro-thymocyte expansion by c-kit and the common cytokine receptor gamma chain is essential for repertoire formation. 907 27

Most mouse thymocytes undergoing positive selection are found on one of two pathways; the c-Kit+ and the c-Kit- pathways. Here, we show that c-Kit and interleukin-7 receptor (IL-7R)-mediated signals support positive selection during the transition from the subpopulation that first expresses cell surface T cell receptor (TCR)-the TCRalpha/betaloCD4(int)/CD8(int) (DPint) c-Kit+ cells to TCRalpha/betamedc-Kit+ transitional intermediate cells (the c-Kit+ pathway). Cells that fail positive selection on the c-Kit+ pathway become TCRalpha/betaloc-Kit- (DPhi) blasts that appear to undergo alternative TCRalpha rearrangements. The rare DPhic-Kit- blast cells that thus are salvaged for positive selection by expressing a self-major histocompatibility complex selectable TCRalpha/beta up-regulate IL-7R, but not c-Kit, and are the principal progenitors on the c-Kit- pathway; this c-Kit-IL-7R+ pathway is mainly CD4 lineage committed. Cell division is a feature of the TCRlo-medc-Kit+ transition, but is not essential for CD4 lineage maturation from DPhic-Kit- blasts. In this view, positive selection on the c-Kit- path results from a salvage of cells that failed positive selection on the c-Kit+ path.
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PMID:Two distinct pathways of positive selection for thymocytes. 948 12

Cryptopatches (CPs) are part of the murine intestinal immune compartment. Cells isolated from CPs of the small intestine that were c-kit positive (c-kit+) but lineage markers negative (Lin-) gave rise to T cell receptor (TCR) alphabeta and TCR gammadelta intestinal intraepithelial T cells after in vivo transfer or tissue engraftment into severe combined immunodeficient mice. In contrast, cells from Peyer's patches and mesenteric lymph nodes, which belong in the same intestinal immune compartment but lack c-kit+Lin- cells, failed to do so. These findings and results of electron microscopic analysis provide evidence of a local intestinal T cell precursor that develops in the CPs.
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PMID:Generation of intestinal T cells from progenitors residing in gut cryptopatches. 956 28

Precursor lymphocytes undergo expansion prior to immunoglobulin (Ig) or T cell receptor (TCR) rearrangements. Development of thymocytes, but not B cells, is entirely blocked in mice lacking both the receptor-tyrosine-kinase c-kit and the common cytokine receptor gamma chain (gamma c). In c-kit-gamma c-mice, TCR beta rearrangements are limited to mono- or oligoclonal DJ junctions. Here, effects of lack of c-kit or gamma c, or both, on the junctional diversity of TCR gamma and delta, and Ig VH(DH)JH loci were analyzed. All rearrangements were present in wildtype and mutant mice. However, sequencing of the junctions revealed monoclonal TCR gamma (V gamma 2 J gamma 1) and TCR delta (V delta 1(D delta)J delta 2) joints in c-kit-gamma c-, but not c-kit+ gamma c- or wildtype thymocytes. In contrast to TCR beta, gamma and delta loci, VHDHJH junctions were more diverse in c-kit-gamma c-mice. Thus, the two analyzed growth factor receptors mediate signaling pathways required for progenitor expansion and generation of junctional diversity at TCR loci, but have less influence on the diversity of IgH junctions.
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PMID:Antigen-receptor junctional diversity in growth-factor-receptor mutant mice. 970 Apr 64


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