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1.
Mucosal Immunol ; 10(2): 481-492, 2017 03.
Article in English | MEDLINE | ID: mdl-27381924

ABSTRACT

Mast cells and basophils are innate immune cells with overlapping functions that contribute to anti-helminth immunity. Mast cell function during helminth infection was previously studied using mast cell-deficient Kit-mutant mice that display additional mast cell-unrelated immune deficiencies. Here, we use mice that lack basophils or mucosal and connective tissue mast cells in a Kit-independent manner to re-evaluate the impact of each cell type during helminth infection. Neither mast cells nor basophils participated in the immune response to tissue-migrating Strongyloides ratti third-stage larvae, but both cell types contributed to the early expulsion of parasitic adults from the intestine. The termination of S. ratti infection required the presence of mucosal mast cells: Cpa3Cre mice, which lack mucosal and connective tissue mast cells, remained infected for more than 150 days. Mcpt5Cre R-DTA mice, which lack connective tissue mast cells only, and basophil-deficient Mcpt8Cre mice terminated the infection after 1 month with wild-type kinetics despite their initial increase in intestinal parasite burden. Because Cpa3Cre mice showed intact Th2 polarization and efficiently developed protective immunity after vaccination, we hypothesize that mucosal mast cells are non-redundant terminal effector cells in the intestinal epithelium that execute anti-helminth immunity but do not orchestrate it.


Subject(s)
Intestine, Small/immunology , Mast Cells/immunology , Strongyloides ratti/immunology , Strongyloidiasis/immunology , Th2 Cells/immunology , Animals , Carboxypeptidases A/genetics , Chymases/genetics , Immunity, Mucosal , Intestine, Small/parasitology , Larva , Mast Cells/parasitology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Parasite Load , Rats , Rats, Wistar , Tryptases/genetics
2.
Nature ; 414(6865): 763-8, 2001 Dec 13.
Article in English | MEDLINE | ID: mdl-11742403

ABSTRACT

The thymus is organized into medullary and cortical zones that support distinct stages of T-cell development. The formation of medulla and cortex compartments is thought to occur through invagination of an endodermal epithelial sheet into an ectodermal one at the third pharyngeal pouch and cleft, respectively. Epithelial stem/progenitor cells have been proposed to be involved in thymus development, but evidence for their existence has been elusive. We have constructed chimaeric mice by injecting embryonic stem (ES) cells into blastocysts using ES cells and blastocysts differing in their major histocompatibility complex (MHC) type. Here we show that the MHC class-II-positive medullary epithelium in these chimaeras is composed of cell clusters, most of which derive from either embryonic stem cell or blastocyst, but not mixed, origin. Thus, the medulla comprises individual epithelial 'islets' each arising from a single progenitor. One thymic lobe has about 300 medullary areas that originate from as few as 900 progenitors. Islet formation can be recapitulated after implantation of 'reaggregated fetal thymic organs' into mice, which shows that medullary 'stem' cells retain their potential until at least day 16.5 in fetal development. Thus, medulla-cortex compartmentalization is established by formation of medullary islets from single progenitors.


Subject(s)
Stem Cells , Thymus Gland/cytology , Animals , Blastocyst/cytology , Cell Differentiation , Cell Line , Cell Lineage , Chimera , Epithelial Cells/cytology , Hematopoietic Stem Cell Transplantation , Histocompatibility Antigens Class II/biosynthesis , Keratins/biosynthesis , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Inbred CBA , Microsatellite Repeats , Organ Culture Techniques , Polymerase Chain Reaction , Thymus Gland/embryology , Thymus Gland/immunology
3.
J Exp Med ; 193(12): 1431-7, 2001 Jun 18.
Article in English | MEDLINE | ID: mdl-11413198

ABSTRACT

The thymus in mice lacking both the receptor tyrosine kinase c-kit and the common cytokine receptor gamma chain (gamma(c)) is alymphoid because these receptors provide essential signals at the earliest stages of thymocyte development. The signals transduced by these receptors potentially regulate proliferation, survival, or differentiation, but the contribution of each receptor to distinct intracellular signaling cascades is only poorly defined. Here, we have examined whether enforced expression of Bcl-2 can rescue thymocyte development in c-kit and gamma(c) single or double mutant mice. A bcl-2 transgene (E(mu)-bcl-2-25; expressed in the T cell lineage) was introduced into (a) c-kit and gamma(c) wild-type (c-kit+gamma(c)+bcl+), (b) c-kit-deficient (c-kit(-)gamma(c)+bcl+), (c) gamma(c)-deficient (c-kit+gamma(c)-bcl+), or (d) c-kit and gamma(c) double-deficient mice (c-kit-gamma(c)-bcl+). The bcl-2 transgene was functionally active in wild-type and c-kit or gamma(c) single mutants, as it promoted survival of ex vivo isolated thymocytes, including pro-T cells. In vivo, however, transgenic Bcl-2 did not release T cell precursors from their phenotypic block and failed to increase progenitor or total thymocyte cellularity in c-kit or gamma(c) single or double mutants. These data argue strongly against a role for Bcl-2 as a key mediator in signaling pathways linked to cytokine and growth factor receptors driving early thymocyte development.


Subject(s)
Proto-Oncogene Proteins c-bcl-2/physiology , Proto-Oncogene Proteins c-kit/physiology , Receptors, Interleukin-7/physiology , T-Lymphocytes/cytology , Thymus Gland/growth & development , Animals , Animals, Newborn , Cell Survival , Hyaluronan Receptors/analysis , Interleukin Receptor Common gamma Subunit , Mice , Mutation , Phenotype , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-kit/genetics , Receptors, Growth Factor/metabolism , Receptors, Interleukin-2/analysis , Receptors, Interleukin-7/genetics , Transgenes
6.
Curr Opin Immunol ; 12(2): 159-65, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10712942

ABSTRACT

Recent studies have begun to unravel some of the molecular pathways that appear to control the processes of T cell determination in the earliest thymocyte precursors. In addition, the analyses of mouse mutants with an entirely alymphoid thymus have shed light on the developmental relationship of pro-T cells and thymic dendritic cells, revealing that development of thymocytes and thymic dendritic cells can be dissociated.


Subject(s)
Gene Expression Regulation, Developmental , Hematopoiesis , Hematopoietic Stem Cells/cytology , Repressor Proteins , T-Lymphocyte Subsets/cytology , Animals , Calcium-Binding Proteins , Cell Differentiation , Cell Lineage , Cytokines/physiology , Dendritic Cells/cytology , Helix-Loop-Helix Motifs , Hematopoiesis/genetics , Hematopoietic Cell Growth Factors/physiology , Humans , Inhibitor of Differentiation Protein 1 , Intercellular Signaling Peptides and Proteins , Membrane Proteins/physiology , Mice , Radiation Chimera , Receptors, Cytokine/physiology , Receptors, Notch , Serrate-Jagged Proteins , Signal Transduction , Thymus Gland/cytology , Transcription Factors/classification , Transcription Factors/physiology , Transcription, Genetic
7.
Proc Natl Acad Sci U S A ; 96(26): 15068-73, 1999 Dec 21.
Article in English | MEDLINE | ID: mdl-10611339

ABSTRACT

Thymocytes and thymic dendritic cell (DC) lineages develop simultaneously and may originate from a common intrathymic progenitor. Mice deficient for two growth factor receptor molecules [c-kit and the common cytokine receptor gamma chain (gamma(c))] lack all thymocytes including T cell progenitors. Despite this lack of pro-T cells, thymic DC compartments were identified in c-kit(-)gamma(c)(-) mice. Thus, c-kit- and gamma(c)-mediated signals are not essential to generate thymic DCs. In addition, pro-T cells do not appear to be obligatory progenitors of thymic DCs, because DC development is dissociated from the generation of thymocytes in these mice. Thymic DCs in c-kit(-)gamma(c)(-) mice are phenotypically and functionally normal. In contrast to wild-type mice, however, thymic DCs in c-kit(-)gamma(c)(-) and, notably, in RAG-2-deficient mice are CD8alpha(neg/low), indicating that CD8alpha expression on thymic DCs is not independent of thymocytes developing beyond the "RAG-block."


Subject(s)
Dendritic Cells/cytology , Hematopoietic Stem Cells/cytology , Proto-Oncogene Proteins c-kit/genetics , T-Lymphocytes/cytology , Thymus Gland/cytology , Thymus Gland/immunology , Animals , Cell Lineage , DNA-Binding Proteins/genetics , Dendritic Cells/immunology , Hematopoietic Stem Cells/immunology , Lymphocyte Culture Test, Mixed , Mice , Mice, Mutant Strains , Organ Size , T-Lymphocytes/immunology , Thymus Gland/growth & development
8.
J Immunol ; 161(9): 4866-74, 1998 Nov 01.
Article in English | MEDLINE | ID: mdl-9794420

ABSTRACT

Expression of the T1 gene, also known as ST2, DER4, and Fit-1, has been shown to be associated with cell proliferation. It gives rise to two different mRNAs that encode a receptor-like protein and a soluble molecule representing the ectodomain of the receptor form. Although T1 is a member of the IL-1R family, its biologic function is currently unknown. In this study, we have analyzed the expression of the T1 surface Ag in murine hemopoietic organs. Mast cells (MCs) were shown to be the only identifiable cell lineage that expressed T1 at high levels. T1 expression was found on cultured bone marrow-derived immature MCs. Similarly, freshly isolated connective tissue-type MCs from the i.p. cavity were also shown to express high levels of T1. Interestingly, the earliest detectable committed MC precursor isolated from fetal blood (FB) at day 15.5 of gestation, but not circulating hemopoietic stem cells in FB, also expresses high level of T1. Since FB promastocytes lack expression of the high affinity IgE receptor (Fc epsilonRI), T1 expression precedes expression of Fc epsilonRI in MC ontogeny. The finding that the T1 Ag is selectively expressed at several stages during development of the MC lineage suggests that this cell surface molecule, in combination with the well-established markers c-Kit and Fc epsilonRI, should be valuable for studying the MC lineage.


Subject(s)
Fetal Blood/cytology , Gene Expression Regulation, Developmental , Hematopoiesis/genetics , Mast Cells/immunology , Membrane Proteins , Protein Biosynthesis , 3T3 Cells/metabolism , Animals , Bone Marrow Cells/immunology , Breast/cytology , Cell Line , Cell Lineage , Epithelial Cells/metabolism , Female , Hematopoietic Stem Cells/immunology , Interleukin-1 Receptor-Like 1 Protein , L Cells/metabolism , Lymphoid Tissue/metabolism , Macrophages/metabolism , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Peritoneal Cavity/cytology , Proteins/genetics , Receptors, IgE/biosynthesis , Receptors, Interleukin
9.
Dev Comp Immunol ; 22(3): 351-65, 1998.
Article in English | MEDLINE | ID: mdl-9700464

ABSTRACT

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.


Subject(s)
Gene Rearrangement, T-Lymphocyte , Genes, Immunoglobulin , Genetic Variation , Proto-Oncogene Proteins c-kit/genetics , Receptors, Antigen, T-Cell, alpha-beta/genetics , Receptors, Antigen, T-Cell, gamma-delta/genetics , Animals , Female , Growth Substances/physiology , Immunoglobulin Joining Region/genetics , Immunoglobulin Variable Region/genetics , Immunoglobulin delta-Chains/genetics , Immunoglobulin gamma-Chains/genetics , Male , Mice , Mice, Inbred BALB C , Mice, Mutant Strains , Proto-Oncogene Proteins c-kit/physiology , Receptors, Antigen, T-Cell, gamma-delta/physiology , Spleen , Thymus Gland
11.
Curr Opin Immunol ; 10(2): 196-207, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9602309

ABSTRACT

The early phases of T-cell development require both cell-cell interactions and soluble factors provided by stromal cells within the thymic microenvironment. Still, the precise nature of the signals delivered in vivo by cytokines (resulting in survival, proliferation or differentiation) remains unclear. Recent studies using mice deficient in cytokines or in their receptors have helped to identify essential signaling pathways required for the development of intrathymic precursors to mature alpha beta and gamma delta T cells. In addition, cytokine requirements for the development of natural killer cells were revealed in such mutants. The results obtained demonstrate that the development of all classes of lymphocytes (natural killer, gamma delta T cells and alpha beta T cells) is cytokine dependent, but the specific requirements differ for each lineage.


Subject(s)
Receptor Protein-Tyrosine Kinases/physiology , Receptors, Cytokine/physiology , T-Lymphocytes/cytology , Animals , Antigens, CD/physiology , Cell Differentiation/physiology , Hematopoiesis/physiology , Humans , Interleukin-7/physiology , Mice , Proto-Oncogene Proteins c-kit/physiology , Receptors, Interleukin/physiology , Receptors, Interleukin-7 , Signal Transduction/physiology , Stem Cell Factor/physiology , Stromal Cells/physiology , T-Lymphocytes/chemistry , Thymus Gland/cytology
13.
Eur J Immunol ; 27(8): 2102-12, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9295051

ABSTRACT

Previous results have shown that pertussis toxin-sensitive Gi proteins are likely to be involved in regulating the emigration of mature thymocytes from the thymus. In this study, a low stringency polymerase chain reaction (PCR) approach was used to identify Gi protein-coupled cell surface receptors expressed in mouse thymocytes. Among the ten G protein-coupled receptor cDNA isolated, the most prevalent cDNA encoded a polypeptide highly homologous to the human leukocyte-expressed seven-transmembrane-domain receptor LESTR, also referred to as HIV entry cofactor, fusin, or CXCR4. Isolation of full-length cDNA revealed that alternative RNA splicing produces transcripts encoding two isoforms of the murine LESTR, differing by the presence of two amino acids in the N-terminal portion of the longer protein. Functional reconstitution of recombinant murine LESTR with recombinant heterotrimeric G proteins in baculovirus-infected insect cells showed that both receptor variants mediate stromal cell-derived factor 1alpha activation of the pertussis toxin-sensitive G protein Gi2. Receptor subtype-specific reverse transcriptase-PCR analysis revealed differential expression of the two receptor mRNA in lymphoid tissues and brain, indicating that distinct functions are mediated by the two receptor isoforms in these tissues. The presence of LESTR mRNA in very early thymocytes as well as in immature (CD4+ CD8+) thymocytes suggests that both CD4 and LESTR are co-expressed and render developing human thymocytes susceptible for HIV entry, which may affect generation of both CD4+ CD8- and CD4- CD8+ mature lineages.


Subject(s)
Chemokines/metabolism , GTP-Binding Proteins/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , Receptors, HIV/genetics , Receptors, HIV/metabolism , Receptors, Immunologic/genetics , Receptors, Immunologic/metabolism , Alternative Splicing , Amino Acid Sequence , Animals , Cattle , Cloning, Molecular , DNA, Complementary/genetics , Gene Expression , Humans , Mice , Molecular Sequence Data , Polymerase Chain Reaction , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Receptors, CXCR4 , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Sequence Homology, Amino Acid , Species Specificity , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism
14.
Immunity ; 6(3): 265-72, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9075927

ABSTRACT

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.


Subject(s)
Hematopoietic Stem Cells/cytology , Proto-Oncogene Proteins c-kit/physiology , Receptors, Cytokine/physiology , T-Lymphocytes/cytology , Animals , B-Lymphocytes/physiology , Cell Differentiation/drug effects , Cell Differentiation/immunology , Clone Cells , Erythropoiesis/immunology , Gene Rearrangement, T-Lymphocyte , Hematopoiesis/immunology , Hematopoietic Stem Cells/drug effects , Mice , Mice, Mutant Strains , Proto-Oncogene Proteins c-kit/genetics , Receptors, Antigen, T-Cell, alpha-beta/genetics , Receptors, Cytokine/genetics , T-Lymphocytes/metabolism , Thymus Gland/cytology , Thymus Gland/metabolism
15.
Blood ; 89(2): 518-25, 1997 Jan 15.
Article in English | MEDLINE | ID: mdl-9002954

ABSTRACT

The receptor-type tyrosine kinase, c-kit is expressed in hematopoietic stem cells (HSC), myeloid, and lymphoid precursors. In c-kit ligand-deficient mice, absolute numbers of HSC are mildly reduced suggesting that c-kit is not essential for HSC development. However, c-kit- HSC cannot form spleen colonies or reconstitute hematopoietic functions in lethally irradiated recipient mice. Based on in in vitro experiments, a critical role of c-kit in B-cell development was suggested. Here we have investigated the B-cell development of c-kit-null mutant (W/W) mice in vivo. Furthermore, day 13 fetal liver cells from wild type or W/W mice were transferred into immunodeficient RAG-2-/- mice. Surprisingly, transferred c-kit- cells gave rise to all stages of immature B cells in the bone marrow and subsequently to mature conventional B2, as well as B1, type B cells in the recipients to the same extent as transferred wild type cells. Hence, in contrast to important roles of c-kit in the expansion of HSC and the generation of erythroid and myeloid lineages and T-cell precursors, c-kit- HSC can colonize the recipient bone marrow and differentiate into B cells in the absence of c-kit.


Subject(s)
B-Lymphocytes/cytology , Proto-Oncogene Proteins c-kit/metabolism , Stem Cell Factor/metabolism , Animals , B-Lymphocytes/metabolism , Cell Differentiation , Flow Cytometry , Gene Expression Regulation, Developmental , Mice , Proto-Oncogene Proteins c-kit/genetics , Stem Cell Factor/genetics
16.
Immunity ; 5(3): 217-28, 1996 Sep.
Article in English | MEDLINE | ID: mdl-8808677

ABSTRACT

We grafted fetal thymi from wild-type mice into immunodeficient RAG-2-/- or class II-/-RAG-2-/- (class II MHC-) recipients and followed the fate of naive CD4+ T cells derived from the grafts. In both types of recipients, newly generated CD4+ T cells proliferated to the same extent in the periphery and rapidly filled the empty T cell compartment. However, CD4+ T cells in class II- recipients gradually decreased in number over 6 months. These results show that interactions between the TCR and class II molecules are not required for newly generated CD4+ T cells to survive and proliferate, but are necessary to maintain the size of the peripheral T cell pool for extended periods.


Subject(s)
CD4-Positive T-Lymphocytes/physiology , Histocompatibility Antigens Class II/physiology , Animals , CD3 Complex/analysis , CD4 Antigens/analysis , Lymphocyte Activation , Mice , Receptors, Antigen, T-Cell, alpha-beta/analysis , Receptors, Antigen, T-Cell, alpha-beta/physiology , Thymus Gland/transplantation
17.
Science ; 271(5250): 818-22, 1996 Feb 09.
Article in English | MEDLINE | ID: mdl-8629001

ABSTRACT

Mast cells originate from hematopoietic stem cells, but the mast cell-committed precursor has not been identified. In the study presented here, a cell population in murine fetal blood that fulfills the criteria of progenitor mastocytes was identified. It is defined by the phenotype Thy-1loc-Kithi, contains cytoplasmic granules, and expresses RNAs encoding mast cell-associated proteases but lacks expression of the high-affinity immunoglobulin E receptor. Thy-1loc-Kithi cells generated functionally competent mast cells at high frequencies in vitro but lacked developmental potential for other hematopoietic lineages. When transferred intraperitoneally, this population reconstituted the peritoneal mast cell compartment of genetically mast cell-deficient W/Wv mice to wild-type levels.


Subject(s)
Hematopoietic Stem Cells/cytology , Mast Cells/cytology , Animals , Base Sequence , Cell Lineage , Cell Transplantation , Cells, Cultured , Cytoplasmic Granules/ultrastructure , Endopeptidases/genetics , Endopeptidases/metabolism , Fetal Blood , Hematopoietic Stem Cells/physiology , Hematopoietic Stem Cells/ultrastructure , Immunophenotyping , Interleukin-3/pharmacology , Mast Cells/physiology , Mast Cells/ultrastructure , Mice , Molecular Sequence Data , Peritoneal Cavity/cytology , Proto-Oncogene Proteins c-kit/analysis , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, IgE/analysis , Receptors, IgE/genetics , Stem Cell Factor/pharmacology , Thy-1 Antigens/analysis
18.
Oncogene ; 12(2): 397-404, 1996 Jan 18.
Article in English | MEDLINE | ID: mdl-8570217

ABSTRACT

The receptor tyrosine kinase Tie1 is expressed in both vascular endothelial cells and immature hematopoietic cells. Expression of a common signaling molecule in distinct cellular lineages may suggest common ancestry of these lineages in ontogeny and/or utilization of shared signaling pathways. Tie 1-deficient mice carrying a targeted insertional mutation in germ line show defects in endothelial cell integrity resulting in edema and hemorrhage. To analyse the potential role of this kinase in hematopoietic cells, we have now compared hematopoietic compartments in wildtype and Tiel-deficient mice. The results show: (1) Total cellularity is mildly reduced comparing Tie1-/- and wildtype fetal liver from day 15.5 of gestation. (2) In vitro colony assays and cell transfer experiments of fetal liver cells into lymphocyte-deficient recombination-activating-gene-2-/- mice reveal that Tie1-/- hematopoietic progenitor cells can generate myeloid lineages as well as T and B lymphocytes. (3) Tie1-/- fetal liver cells contain long-term (at least 4 months) bone marrow-reconstituting hematopoietic stem cells suggesting that this kinase is not critical for stem cell-engraftment nor self-renewal.


Subject(s)
Endothelium, Vascular/cytology , Hematopoiesis , Receptor Protein-Tyrosine Kinases/physiology , Animals , Base Sequence , Bone Marrow Cells , Hematopoietic Stem Cells/physiology , Interleukin-3/pharmacology , Lymphocytes/physiology , Macrophage Colony-Stimulating Factor/pharmacology , Mice , Molecular Sequence Data , Receptor, TIE-1 , Receptors, TIE , Stem Cell Factor/pharmacology
19.
Immunity ; 3(3): 313-9, 1995 Sep.
Article in English | MEDLINE | ID: mdl-7552996

ABSTRACT

To investigate the role of the receptor-type tyrosine kinase, c-kit and its ligand, stem cell factor (SCF) in T cell development, we analyzed c-kit (W/W) and SCF (SI/SI) deficient mice. We also engrafted wild-type or SCF-deficient fetal thymi onto wild-type recipient mice and analyzed the rate of proliferation by in vivo bromodeoxyuridine labeling. The results show that the most immature thymocyte compartment defined as CD3-CD4-CD8- is significantly reduced in SI/SI grafts and W/W thymi compared with wild-type counterparts. Also, the expansion rate of these immature thymocytes in SI/SI graft is reduced by -50%. These experiments provide direct evidence for an important role for c-kit-SCF interactions in expansion of very early thymocytes.


Subject(s)
Stem Cell Factor/physiology , T-Lymphocytes/physiology , Animals , Base Sequence , Bromodeoxyuridine/metabolism , CD4 Antigens/analysis , CD8 Antigens/analysis , Cell Movement , Mice , Mice, Inbred C57BL , Molecular Sequence Data , Stem Cell Factor/genetics
20.
Eur J Immunol ; 25(7): 1877-82, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7621864

ABSTRACT

We have analyzed pre-T cell receptor alpha (pT alpha) gene expression in cells from various anatomical sites to investigate the lineage specificity of pT alpha RNA as well as its presence in pro-T cells and in sites of extrathymic T cell development. pT alpha RNA is found in precursors of alpha beta T cells but is absent from mature alpha beta T cells as well as T cells that express the gamma delta T cell receptor on the cell surface. pT alpha expression is exquisitely T lineage specific in that mature and immature B cells, myeloid cells, NK cells and pluripotent stem cells are pT alpha negative. On the other hand, pT alpha expression is found in pro-T cells outside the thymus as well as in intra- and extra-thymic sites of T cell development. The latter finding is consistent with the notion that early steps of T cell development within and outside the thymus may be similar.


Subject(s)
Receptors, Antigen, T-Cell, alpha-beta/genetics , T-Lymphocytes/physiology , Thymus Gland/cytology , Animals , Base Sequence , Cell Differentiation , DNA Primers/chemistry , Gene Expression , Hematopoietic Stem Cells/cytology , Hematopoietic Stem Cells/metabolism , Lymph Nodes/metabolism , Mice , Mice, Inbred C57BL , Mice, Nude , Molecular Sequence Data , Spleen/metabolism , T-Lymphocytes/cytology
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