Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.148 (Thy1)
 1,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gamma-irradiation of plateau phase cultures of the clonal murine bone marrow stromal cell line D2XRII followed by cocultivation of a clonal interleukin 3 (IL-3) (granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent hematopoietic progenitor cell line FDC-P1JL26 results in a significant increase in "cobblestone islands" of attachment and emergence of subclonal factor-independent malignant sublines. Biochemical purification of conditioned medium from irradiated D2XRII cells yielded a 75,000-dalton glycoprotein termed leukemogenic stromal factor (LSF) that was neutralized by a polyclonal antiserum to murine macrophage colony-stimulating factor (M-CSF). A monoclonal antibody to the murine M-CSF receptor (c-fms) neutralized the biological activity of this molecule in a manner comparable to its effect on recombinant human or murine M-CSF. FDC-P1JL26 parent cells were positive for Ly5, MEL-14, mGR, VLA-4, PGP-1 (CD44), and Thy1.2. After culture in LSF, Thy1.2, MEL-14, and mGR became undetectable; however, significant cell surface MAC-1 antigen and c-fms (M-CSF receptor) were expressed. Neither line was positive for Ly6, Ly22, I-CAM-1, or B220 antigen. LSF-precultured FDC-P1JL26 cells transferred as single cells to microwell culture with 5000-cGy-irradiated D2XRII cells revealed a 60-fold increase in frequency of cobblestone island formation and evolution of factor-independent subclones compared to the parent line. Both parent and LSF-precultured cells became factor independent at a 100-fold lower frequency if kept in suspension in LSF in the absence of stromal cells. Antiserum to M-CSF or monoclonal antibody to the murine M-CSF receptor (c-fms) did not inhibit or displace cobblestone island formation by either clone of FDC-P1 on irradiated stromal cells indicating a mechanism of binding not involving the M-CSF receptor. However, anti-serum to the M-CSF receptor inhibited growth of one factor-independent subclone. In separate studies, a subclone of IL-3-dependent 32Dc13 cells, expressing the transfected murine c-fms protooncogene but not the parent 32Dc13 cell line or another subclone expressing the transfected gene for the human M-CSF receptor, showed adherence and became factor independent when cocultivated with irradiated D2XRII stromal cells. Thus, irradiated stromal cells bind M-CSF receptor-positive hematopoietic progenitor cells and induce c-fms-dependent factor-independent tumorigenic subclones. The cellular interactions in this model may be relevant to gamma-irradiation leukemogenesis in vivo.
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PMID:Humoral and cell surface interactions during gamma-irradiation leukemogenesis in vitro. 153 94

Aging is associated with a decrease in the functional activity of T cells. We have explored age-related alterations in CD44 and MEL-14 expression by spleen cells bearing the Thy1.2, CD4 or CD8 antigens in C57BL/6 mice at 2, 8, 15 and 23 months of age. The membrane expression of CD44 and MEL-14 molecules can be used to distinguish naive (CD44low, MEL-14high) from preactivated/memory (CD44high, MEL-14low) T cells. Our results show that the proportion of CD4+ splenic cells begins to decrease at an intermediate age (8-month-old mice), whereas the proportion of CD8+ cells remains unaltered. The proportion of CD4+ and CD8+ splenic cells with the CD44high memory phenotype was increased at an early stage of aging (in 8-month-old mice) without a concomitant change in MEL-14 expression. In older mice, MEL-14 expression decreased on CD4+ but not on CD8+ subsets. Recent studies have reported that following activation, the expression of CD44 molecules containing additional, so-called variable exons can be detected. By PCR, we observed an increase in CD44 transcripts containing the v6 or v7 variable exons in murine lymph nodes at the age of 15 months. Our results suggest that v6- or v7-containing variants of CD44 may be involved in the development of memory cells. Taken together, these results suggest that the trafficking of memory T cells in aging may be altered by quantitative and/or qualitative differences in the expression of molecules involved in lymphocyte recirculation.
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PMID:Quantitative and qualitative changes in CD44 and MEL-14 expression by T cells in C57BL/6 mice during aging. 756 10

So far all studies on the murine ageing process have been conducted on virgin mice. Immune ageing may be influenced by sex hormone differences related to sex or pregnancies. The aim of this study was to investigate whether pregnancies and gender influence the cell changes observed during ageing in a peripheral lymphoid compartment of C57B1/6 mice. Using flow cytometry, changes in (Thy1.2+) T cell, (B220+) B cell and (CD 11b/Mac-1) macrophage spleen populations were monitored in 2, 8 (3 months after last pregnancy) 15 and 23-month-old mice including males, virgin and multiparous females. The development of naive (CD44(low)), memory (CD44(high)), activated/memory (MEL-14, CD62L) cells were investigated in CD4+ and CD8+ T cell subsets. Both short term (at 8 months) and long term (at 15 and 23 months) effects of multiparity were obvious in the lymphocyte/macrophage population changes associated with the ageing process. Short-term effects included delayed appearance of CD4+CD44(high) memory lymphocytes and increased numbers of both CD4+MEL-14(1ow) activated/memory cells and Mac-1+ macrophages when compared with virgin control mice. Later effects of multiparity were increased CD8alpha(dull) populations and increased T/B cell ratios and the ratio of memory to naive CD4+ cells (CD44+(high)/CD44+(low). A sex effect was noticed: males exhibited lower Mac-1+ levels and memory/naive ratio in CD4+ subset than virgin females throughout life. These results suggest that gender and/or pregnancies affect the age-related distribution of lymphoid and macrophage cell populations in the spleen of C57B1/6 mice.
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PMID:Surface antigen expression in spleen cells of C57B1/6 mice during ageing: influence of sex and parity. 906 39

Thymic function is severely impaired in most marrow transplant recipients. To evaluate the impact of thymic hypoplasia on T cell reconstitution following marrow transplantation, we compared the phenotype and function of T lymphocytes in thymectomized recipients with those of euthymic hosts. Irradiated C57BL/6 mice (Thy1.2+, Ly5.1+) received 10(7) T cell-depleted B6.Ly5.2 bone marrow cells (Thy1.2+, Ly5.2+), with or without 3 x 10(5) B6.PL lymph node cells (Thy1.1+, Ly5.1+) as a source of T lymphocytes. Multiparameter flow cytometry analysis showed that in euthymic mice (group 1), T cell reconstitution was carried out by donor hematopoietic stem cells that differentiated in the host's thymus, whereas the production of chimeric T cells in athymic recipients depended on the presence or absence of T cells in the graft. When T lymphocytes were present in the graft (group 2), their progeny constituted the vast majority of splenic T cells on day 100 posttransplant. When the graft did not contain T lymphocytes (group 3), T cell reconstitution resulted from extrathymic maturation of donor hematopoietic progenitors; T cells differentiating along this pathway expressed lower levels of T cell receptor and a large proportion of the CD8+ subset expressed CD8alpha alpha homodimers. The T cell receptor Vbeta profile of all chimeras was similar to that of normal C57BL/6 mice. Compared with T cells found in euthymic recipients, those in mice from groups 2 and 3 were less abundant (particularly with respect to the CD4+ subset), displayed the CD44/CD45 phenotype of activated memory cells, and expressed high levels of IL-2 receptor beta chain. These results show that both the presence or absence of the thymus and the composition of the grafted inoculum determine the source and extent of posttransplant T cell reconstitution. Because they determine the nature of the differentiation pathway taken during T cell development in the host, these two factors can exert a critical influence on the appearance of graft vs. host disease and the level of host immunocompetence.
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PMID:Thymic and extrathymic differentiation and expansion of T lymphocytes following bone marrow transplantation in irradiated recipients. 925 13

We have identified a small subset of CD3(+), CD4(+), CD8(-) thymocytes that do not express Thy1 (CD90). This Thy1(-) subset represents 1-3.7% of the total number of thymocytes in a naive mouse. CD4(+)Thy1(-) thymocytes express high levels of CD3, intermediate to high levels of heat-stable antigen (HSA), and low levels of CD25, CD45RB, CD69, CD44 and CD62L. They produce high titers of IL-4 and no IFN-gamma upon stimulation in vitro, a response characteristic of T(h)2 cells. In the thymi of mice infected neonatally with a high dose of the retrovirus Cas-Br-E MuLV, the frequency of CD4(+)Thy1(-) cells increased approximately 10-fold. High-dose virus infection resulted in decreased HSA and increased CD44 expression on CD4(+)Thy1(-) cells relative to cells from naive mice. CD4(+)Thy1(-) cells from high-dose infected mice also secreted IL-4 and not IFN-gamma upon in vitro stimulation. We previously reported that infection of newborn mice with a high dose of murine retrovirus results in the induction of a non-protective anti-viral T(h)2 T cell response; CD4(+)Thy1(-) thymocytes with a T(h)2-like cytokine profile may play a role in determining the cytokine bias of this anti-viral response.
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PMID:CD4+Thy1- thymocytes with a Th-type 2 cytokine response. 1113 36

T cells that emigrate from the thymus have primarily been studied in vivo using fluorescent dye injection of the thymus. This study examined the properties of thymocytes that emigrate from cultured thymic lobes in organ culture. Under these conditions, thymic emigrants displayed the expected phenotype, that of mature thymocytes expressing high levels of T-cell receptor (TCR-alphabeta) and either CD4 or CD8, and were observed to emigrate within 24 hours of positive selection. Emigration was inhibited by cytochalasin D, pertussis toxin, or Clostridium difficile toxin B, implicating an active motility process. Most of the surface markers on alphabeta-thymic emigrants (Thy1, CD44, CD69, CD25, leukocyte functional antigen-1, intercellular adhesion molecule-1, alpha(4)-integrin, alpha(5)-integrin, CD45, and CD28) were expressed at a surface density similar to that on mature intrathymic cells and peripheral splenic T cells. Heterogeneous expression of L-selectin and heat-stable antigen (HSA) suggested that subsets emerge from the thymus with a commitment to different migration patterns. The only marker on emigrants not found on either intrathymic cells or mature spleen T cells was CTLA-4, which could dampen the response of emigrants to peripheral antigens. Antigen responsivenes measured in vitro against allogeneic dendritic cells showed a proliferative response comparable to that of splenic T cells. In vivo, however, thymic emigrants failed to induce an acute graft-versus-host reaction in allogeneic severe combined immunodeficiency recipients. This suggests that a mechanism operating in vivo, perhaps tolerance or migration pattern, attenuates the response of emigrants against antigens that did not induce their deletion in the thymus.
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PMID:Thymic emigrants isolated by a new method possess unique phenotypic and functional properties. 1122 81

Common lymphoid progenitors (CLP) are generated in adult bone marrow (BM), but the intermediate steps leading to T cell commitment are unknown, and so is the site at which this commitment occurs. Here, we show that colonies arising in the spleen 12 days after BM injection harbor T cell precursors that are undetectable in BM. These precursors did not generate myeloid cells in vivo but repopulated the thymus and the peripheral T cell compartment much faster than did CLP. Two lineage negative (Lin(-)) subpopulations were distinguished, namely CD44(+) Thy1(-) cells still capable of natural killer generation and transient low-level B cell generation, and T cell-restricted CD44(-) Thy1(+) cells. At a molecular level, frequency of CD3epsilon and preTalpha mRNA was very different in each subset. Furthermore, only the CD44(-) Thy1(+) subset have initiated rearrangements in the T cell receptor beta locus. Thus, this study identifies extramedullary T cell progenitors and will allow easy approach to T cell commitment studies.
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PMID:Major T cell progenitor activity in bone marrow-derived spleen colonies. 1192 35

A transgenic reporter mouse strain, which expressed the human CD25 (hCD25) surface marker as a reporter under the control of the pre-T cell receptor alpha(pTalpha) promoter, was used to identify lymphoid precursors that expressed pTalpha intracellularly. The hCD25 reporter marked intra- and extrathymic precursors of lymphocytes but not myeloid cells. The earliest intrathymic precursors were CD4(lo)CD8(-)CD25(-)CD44(+)c-Kit(+) cells that expressed elevated levels of Notch-1 mRNA. Clonogenic assays showed that the extrathymic precursors were common lymphoid progenitors (CLPs) that included CD19(-), B220(+), Thy1(+) and CD4(+) cells. Thus, the pTalpha reporter can be used to trace lymphopoiesis between CLPs and alphabeta T cells. The slower extinction of the hCD25 reporter compared to pTalpha enabled us to define points at which pTalpha(-) lineages branched off.
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PMID:Tracing lymphopoiesis with the aid of a pTalpha-controlled reporter gene. 1192 10

Recent studies have shown that apoptotic cell death associated with selection for thymocytes that express clonotypic TCRbeta or TCRgammadelta proteins takes place in the DN4 (CD44-CD25-) subset of CD4-CD8- double negative (DN) thymocytes. A detailed analysis of the DN4 subset is therefore of interest. Using intracellular (IC) staining for clonotypic TCR and CD3varepsilon proteins we find that DN4 cells consist of five subpopulations: TCRbetaIC(high)/CD3varepsilonIC(high)/TCRgammadeltaIC-, TCRbetaI-C-/CD3varepsilonIC(high)/TCRgammadeltaIC(+), TCRbetaIC(high)/CD3varepsilonIC(high)/TCRgammadeltaIC(+), TCRbetaIC(low)/CD3varepsilonIC(low)/TCRgammadeltaIC(-), and TCRbetaIC(-)/CD3varepsilonIC(-)/TCRgammadeltaIC(-). Expression levels of IC TCRbeta/CD3varepsilon, and of Thy1.2, CD2, and CD69 at the cell surface suggest that the TCRbetaIC(low)/CD3varepsilonIC(low)/TCRgammadeltaIC(-) subset harbors the direct precursors of DP cells, and is critical for life/death decisions in early thymic selection. TCRbeta/CD3varepsilon downregulation is less pronounced in DN4 and DP cells of mice deficient for CD3zeta or for p56(lck), suggesting that the dynamics of TCR protein regulation in the DN4 subset is dependent on CD3 signaling.
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PMID:Heterogeneity of the DN4 (CD44-CD25-) subset of CD4-CD8- double negative thymocytes; dependence on CD3 signaling. 1200 43

C3H/He mice produce myeloid leukemias after whole body irradiation of 1-3Gy as compared with non-irradiated controls that produce fewer than 1% of leukemia [Radiatiton Research 127 (1991) 146]. Thus, p53-deficient C57BL/6 strain, a malignant lymphoma prone, was crossed back into C3H/He strain. Lethally irradiated wild-type mice to which p53-deficient bone marrow cells were transplanted (transplantation assay) showed dramatic change in the propensity of leukemia of myeloid lineages, the cells lacking CD3, Thy1.2, sIgM, B220, Mac-1, Gr-1, but being positive for c-Kit and CD44. Furthermore, transplanted mice subjected to 3Gy irradiation gave rise to a faster development of leukemia and a higher frequency of double-lineage leukemias than the non-irradiated control.
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PMID:Stem-cell leukemia: p53 deficiency mediated suppression of leukemic differentiation in C3H/He myeloid leukemia. 1244 80


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