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F Takei

Publications and source records attributed to F Takei.

At least 73 records · Page 4Linked to original sources
PubMed1992

Dual role of IL-7 in the growth and differentiation of immature thymocytes.

The effects of interleukin 7 (IL-7) on subpopulations of CD4-CD8- thymocytes from young adult mice were tested in vitro. When highly purified CD3-CD4-CD8-thymocytes were cultured in the presence of recombinant IL-7, significant proportions of them became CD4+ and/or CD8+ within a day. CD3+ cells were also detected after 2 days. CD3-CD4-CD8- thymocytes were further subdivided into interleukin 2 receptor (IL-2R)- and IL-2R+ populations. The majority of the IL-2R- cells became CD4+ and/or CD8+ in 1 day in the presence of IL-7, and a substantial proportion of them also became CD3+ in 2-3 days. No significant number of CD4+ or CD8+ cells were generated from the IL-2R+ population under the same conditions. However, a small but significant proportion of them became CD3+ in 3-day cultures with IL-7. Although CD4+/CD8+ cells were also generated from the IL-2R- population in 1-day cultures in the absence of IL-7, the viability of the cells declined rapidly, and no significant numbers of CD3+ cells were generated. In proliferation assays, IL-7 alone vigorously stimulated relatively minor subpopulations of CD4-CD8- thymocytes. The IL-7-responsive cells were CD3+, did not express the IL-2R or the heat-stable antigen M1/69, and included both T-cell receptor (TCR)alpha beta + and TCR alpha beta- populations, the latter most likely TCR gamma delta +. The CD3+CD4-CD8- thymocytes, stimulated with IL-7 for 3 days, remained CD4-CD8-. These results demonstrate important roles of IL-7 in the growth and differentiation of CD4-CD8- thymocytes in vitro. It functions as a survival factor and allows CD3-CD4-CD8- cells to undergo their precommitted differentiation without inducing their proliferation, and it also stimulates CD3+CD4-CD8-thymocytes to proliferate without inducing their differentiation.

Animals↗
PubMed1991

Chemically modified antigen-presenting cells induce T lymphocyte allospecific hyporesponsiveness.

We have investigated the interaction between murine T lymphocytes and allogeneic APC in an in vitro proliferative mixed leukocyte reaction. Our results demonstrate that freshly isolated potentially alloreactive murine splenic T lymphocytes, in primary culture, can be induced to develop a state of allospecific proliferative hyporesponsiveness in vitro by exposure to 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide-modified allogeneic APC, a method similar to that previously used to induce nonresponsiveness in murine Ag-specific self-MHC-restricted T lymphocyte clones. This hyporesponsiveness was: specific for the allohaplotype of inducing APC, maintained for 96 h in vitro, not due to cellular inhibitory mechanisms, and associated with reduced ability to secrete IL-2 but not IL-3. Induction of this hyporesponsiveness was not due to altered expression of class II MHC gene products on the APC but was associated with markedly reduced T lymphocyte-APC adhesive interactions despite the lack of a detectable immunophenotypic change in lymphocyte function-associated Ag 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) expression on the modified APC. Therefore, we propose that TCR occupancy in the absence of normal T lymphocyte-APC adhesive clustering may induce T lymphocyte tolerance.

Animals↗
PubMed1991

Ly-49 multigene family. New members of a superfamily of type II membrane proteins with lectin-like domains.

Ly-49 (YE1/48, A1) is a dimer protein expressed on subpopulations of murine NK cells. It is a member of a superfamily of type II transmembrane proteins containing carbohydrate recognition domains (CRD). In the mouse genome, the detection of multiple restriction fragments that cross-hybridize with Ly-49 cDNA probes suggests the presence of related genes. In this study, we have isolated several genomic clones encoding portions of CRD sequences highly homologous to the CRD of Ly-49. By using primers based on the consensus sequences of the genomic clones, expression of Ly-49-related genes was detected by the polymerase chain reaction in various organs, including lung, kidney, liver, spleen, and thymus. Two full-length cDNA clones that are highly homologous to the Ly-49 gene were subsequently isolated from a lung cDNA library. At the nucleotide level, the two clones are 72% and 80% identical to Ly-49 in their translated regions, but their sequences are different from those of the genomic clones characterized to date. The two cDNA clones potentially encode type II transmembrane proteins containing CRD that are very similar to Ly-49. These amino acid sequences are also homologous to other members of the superfamily of CRD-containing type II transmembrane proteins, including hepatic lectins and the low affinity IgER (CD23). The homology is most evident in the CRD but is also significant in other domains. These results demonstrate the existence of several functional genes that are highly related to Ly-49. These genes comprise a subfamily within the superfamily of type II transmembrane proteins containing CRD.

Amino Acid Sequence↗
PubMed1991

Characterization of pancreatic islet cell infiltrates in NOD mice: effect of cell transfer and transgene expression.

Insulin-dependent diabetes mellitus can be transferred into young irradiated non-obese diabetic (NOD) mice by spleen cells from a diabetic NOD donor. T cells (both L3T4+ and Ly-2+) enter the pancreas 2 weeks following transfer. They are present initially at peri-islet locations but progressively infiltrate the islet with accompanying beta cell destruction. The infiltrate is heterogeneous with respect to V beta usage. Inflammatory macrophages (Mac-1+, F4/80+) can be detected at peri-islet locations at 1 week after transfer and continue to be recruited during the disease process. Their presence at the initiation of disease suggests that their primary function may be autoantigen presentation. Increased expression of major histocompatibility complex (MHC) class I molecules is observed on both endocrine and exocrine tissue in areas of intra-islet infiltration. MHC class II and ICAM-1 expression was restricted to the cells constituting the inflammatory infiltrate. Expression of these molecules was not observed on beta cells implying that presentation of autoantigen by the beta cell itself does not play a role in the beta cell destruction in NOD mice.

Animals↗
PubMed1991

Late administration of monoclonal antibody to leukocyte function-antigen 1 abrogates incipient murine cerebral malaria.

We analyzed the role of adhesion molecules in the pathogenesis of experimental cerebral malaria (ECM), since tumor necrosis factor (TNF) plays a major role in this condition and has been shown to up-regulate in vitro expression of cell adhesion molecules (CAM), particularly intercellular CAM-1 (ICAM-1). We found increased expression of ICAM-1 on brain endothelial cells from mice with ECM. Treatment with monoclonal antibodies (mAb) directed against leukocyte function-antigen 1 (LFA-1, the ligand of ICAM-1) on days 6, 8 and 10 almost totally prevented ECM, while decreasing blood TNF levels. To exclude the possibility that the effects of anti-LFA-1 mAb resulted from an even partial inhibition of TNF overproduction, mice with signs of imminent death (hypothermia and neurologic defects) were treated with the anti-LFA-1 mAb, with dramatically protective effect. In contrast, injection of anti-ICAM-1 mAb on day 6 caused rapid death, while it was innocuous in normal mice. An mAb directed against complement receptor type 3 (CR3) was ineffective, as were injections of soluble human ICAM-1. These results suggest that adhesion of LFA-1+ cells to endothelial cells, stimulated by TNF to express high levels of ICAM-1, is critical in the pathogenesis of ECM. Emergency therapy at interfering with cytoadherence could be considered in the treatment of cerebral malaria in man, in which high blood TNF levels are also observed.

Animals↗
PubMed1991

Expression and induction of intercellular adhesion molecules (ICAMs) and major histocompatibility complex (MHC) antigens on cultured murine oligodendrocytes and astrocytes.

Expression of intercellular adhesion molecule-1 (ICAM-1), ICAM-2-like molecule (Lgp55), and class I/II major histocompatibility complex (MHC) antigens (H-2 and Ia) was investigated in cultures of murine oligodendrocytes and astrocytes. Under unstimulated conditions, low levels of ICAM-1 expression were observed on astrocytes (less than 20%), but not on oligodendrocytes. Lgp55 was expressed intensely on oligodendrocytes (greater than 90%) and to a lesser degree on astrocytes (greater than 70%). A weak class I MHC (H-2) immunoreactivity was identified on both oligodendrocytes and astrocytes (50-70%). Class II MHC (Ia) antigen was undetectable on both cell types. After 48-hr exposure to immune mediators that include interferon-gamma (IFN-gamma), 500 U/ml, and supernatant from concanavalin A (Con A)-activated spleen cells, ICAM-1 expression was markedly increased on astrocytes (greater than 80%), but not on oligodendrocytes. Lgp55 expression on both cell types was not altered. Induction of H-2 antigen expression by immune mediators was quite high on both cell types (greater than 95%), while Ia antigen induction was low on astrocytes (less than 50%) and did not occur on oligodendrocytes. Cell type-specific expression and induction of ICAMs and MHC antigens by immune mediators may play roles in lymphocyte-glial cell interactions at the sites of inflammation in the central nervous system (CNS).

Animals↗
PubMed1991

A miniature Clark-type oxygen electrode using a polyelectrolyte and its application as a glucose sensor.

A miniature Clark-type oxygen electrode was fabricated by anisotropically etching silicon. A two-gold-electrode configuration was used and a double-layered gas-permeable membrane was formed directly on the electrolyte, poly(vinyl-4-ethylpyridinium bromide) in the sensitive area. These materials improved the electrode's stability in long-term storage and sterilization tolerance to a practical level. The 90% response time averaged 80 s and residual current 10%, with a good linear calibration curve. The oxygen electrode was also used to make an integrated sensor for the simultaneous determination of glucose and oxygen. The glucose sensor's response time was 50-110 s, with good linearity in glucose concentrations between 56 microM and 1.1 mM at 37 degrees C, pH 7.0.

Biosensing Techniques↗
PubMed1991

Reduction in the severity of graft-versus-host disease and increased survival in allogenic mice by treatment with monoclonal antibodies to cell adhesion antigens LFA-1 alpha and MALA-2.

Bone marrow transplantation is a therapeutic treatment for many life-threatening hematologic disorders, especially leukemia and certain immune deficiency diseases. However, acute graft-versus-host disease is often associated with bone marrow transplantation. In mice, allogeneic GVHD appears to be mediated by both host natural killer cells and donor T cells. In vitro and in vivo experiments demonstrate that treatment with either YN1/1.7 or M17/4.2 mabs is immunomodulatory and inhibits both the mixed lymphocyte reaction and natural killer cell activity. In addition, utilizing an allogeneic model of acute, lethal GVHD with C57B1/6 mice as donors and sublethally irradiated BDF1 mice as recipients, treatment of host mice with anti-LFA-1 alpha (M17/4.2) or anti-MALA-2 (YN1/1.7) mabs at a dose of 10 mg/kg/day for 10 days significantly reduced GVHD and enhanced survival. Mabs to lymphocyte adhesion molecules such as LFA-1 alpha and MALA-2 may provide a useful therapy for the treatment of GVHD.

Animals↗
PubMed1990

Expression cloning of a cDNA encoding M1/69-J11d heat-stable antigens.

The differentiation Ag identified by the mAb M1/69 and J11d (commonly referred to as heat-stable Ag) are found in structurally heterogeneous forms on the surfaces of many types of murine hemopoietic cells. The extinction of expression of these antigens is associated with thymocyte maturation and Ig class switching in B cells, as well as terminal differentiation of macrophages. A cDNA encoding the M1/69-J11d peptide was cloned from a hemopoietic progenitor cell line by immunoselection of COS cells transfected with expression libraries. The cloned cDNA is a copy of a gene that is transcribed in M1/69-J11d+ lymphoid, myeloid, and erythroid cells. This gene could be responsible for the expression of all forms of the M1/69-J11d Ag, although there are homologous genes that may encode some forms of the Ag that are specifically expressed in bone marrow. The cloned cDNA encodes a surprisingly small peptide, predicted to contain only 30 amino acids after removal of a signal sequence and displacement of the C-terminal region by the glycosyl-phosphatidylinositol group that anchors the peptide to the cell surface. Almost all of the mass of the M1/69-J11d Ag accumulates through extensive N- and O-linked glycosylation at multiple sites in the short peptide. These carbohydrates are likely to execute the functions of M1/69-J11d Ag, which could be specialized to each cell type as a consequence of differential glycosylation.

Amino Acid Sequence↗
PubMed1990

Role of ICAM-1 in antigen presentation demonstrated by ICAM-1 defective mutants.

We report a methodology for selecting APC with mutations that have impaired their ability to present Ag to T cells. A20 B lymphoblastoid cells were mutagenized and then repeatedly cocultured with murine T-T hybridomas in the presence of specific Ag. During these cocultures, the T-T hybridomas kill the competent APC, allowing the outgrowth of inactive variants. Two variants, A20.M1 and A20.M2, were isolated and studied in detail. These variants are impaired in their ability to present multiple Ag to T cells. This defect is also observed for the presentation of processing independent peptides by fixed APC indicating that a lesion exists in a post-Ag processing step. The level of expression of MHC molecules is unaffected and the functional defect in the APC is not localized to a particular MHC molecule. In contrast, these mutants were found to have a selective decrease in the expression of the murine homolog of ICAM-1, and the residual ability of these cells to present Ag was not blocked by anti-ICAM-1 mAb. Conversely, Ag presentation by the wild-type A20 is inhibited by anti-ICAM-1 mAb. Similarly, anti-LFA-1 mAb inhibited the response of T cells to Ag presented by the wild-type A20 to a much greater degree than by the mutant cells, indicating that LFA-1 is involved in interaction of T cells with the former, but not latter, APC. In the apparent absence of a contribution of LFA-1 to the T cell-APC interaction, either as a result of mAb blocking or the disruption of the APC membrane, the mutant and wild-type APC have a similar level of Ag-presenting activity. Reconstitution of ICAM-1 expression in these mutants by transfection with murine ICAM-1 cDNA fully restores their ability to present Ag. Together these results demonstrate that a murine ICAM-1 homolog is expressed on A20 B cells, where it functions as a major cell interaction molecule. The degree of functional impairment in these mutant APC gives insight into the contribution of cell interaction molecules to efficient Ag presentation and T cell-B cell interaction. Finally, these results also demonstrate the feasibility of selecting APC with mutations affecting Ag presentation.

Animals↗
PubMed1990

Differing regulation and function of ICAM-1 and class II antigens on renal tubular cells.

Intercellular adhesion molecule-1 (ICAM-1) and MHC class II (Ia) antigens are increased on proximal tubular epithelial cells (TEC) in autoimmune nephritis and transplant rejection. ICAM-1 is a member of the immunoglobulin gene superfamily that increases the avidity of T cell interactions with antigen-presenting cells bearing Ia antigens. Using an existing mAb and cDNA probe for Ia antigen, and a newly described mAb (YN1/1.7.4) and cDNA probe for murine ICAM-1, we compared mRNA transcript levels, surface expression and function of these molecules in transformed TEC derived from normal (C3H/FeJ) and autoimmune (MRL-lpr) mice. No differences were found on TEC between these strains of mice. Stimulation of TEC with interferon-gamma (IFN-gamma) resulted in the expression of Ia antigens, and a marked increase of ICAM-1 from basal levels. Increases in ICAM-1 levels occurred with concentrations of IFN-gamma 10 to 100 times lower (0.5 to 1.0 U/ml) than those required for Ia expression, and preceded Ia antigen expression by more than 48 hours. Anti-ICAM-1 mAb lowered the binding and antigen-presenting ability of TEC to the A2A2 T cell hybridoma, suggesting a role for ICAM-1 in immune interactions between TEC and T cells. Dexamethasone treatment of MRL-lpr mice abrogated the increase of Ia antigens found in the kidneys of nephritic mice yet did not reduce the expression of ICAM-1 in either kidneys or cultured stimulated TEC. We conclude that elevated ICAM-1 expression on TEC increases the immune accessory cell capability of TEC bearing Ia antigens, and is resistant to down-regulation by some immunosuppressive agents.

Animals↗
PubMed1990

Mesangial cell accessory functions: mediation by intercellular adhesion molecule-1.

Mesangial cell (MC) proliferation is an early pathologic alteration characteristic of many forms of immune mediated glomerulonephritis. The intracapillary position, contractile capacity, and production of cytokines and other inflammatory molecules place MC in a pivotal position to initiate, mediate, and direct glomerular damage. We as well as others have noted increased levels of cytokines including IFN gamma, TNF, and IL-1 and the cell surface MHC class II and ICAM-1 molecules in the kidneys of mice with lupus nephritis. MHC class II and ICAM-1 molecules are central to the interaction of T cells with antigen presenting cells (APC). Since cytokines can increase both MHC class II and ICAM-1 molecules, we investigated whether mesangial cells could function as APC or accessory cells after cytokine stimulation. For these studies we established a permanent MC line through transformation with origin-deficient SV40 DNA. Surface expression of ICAM-1 was similar in untransformed MC as well as SV40 transformed MC from normal mice and in untransformed cells from mice with lupus nephritis. Basal expression of ICAM-1 was upregulated rapidly by IFN gamma, TNF, and IL-1. MHC class II expression could not be induced with TNF or IL-1 alone but required prolonged stimulation with IFN gamma. MC adhered and presented antigen to an antigen specific IaK restricted T cell hybridoma. Anti-ICAM-1 mAb decreased adhesion and antigen presentation of cytokine stimulated MC. By comparison, MHC class II mAb abrogated antigen presentation by MC bearing MHC class II but did not block adhesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Intercellular adhesion molecule-1 (ICAM-1) expression is upregulated in autoimmune murine lupus nephritis.

Intercellular adhesion molecule-1 (ICAM-1) is a cell-surface protein regulating interactions among immune cells. To determine whether altered expression of ICAM-1 occurs in autoimmune lupus nephritis, we studied ICAM-1 expression in kidneys of normal and autoimmune MRL-lpr and (NZBX NZW)F1 (NZB/W) mice. By immunoperoxidase staining, ICAM-1 is constitutively expressed at low levels in proximal tubules (PT), endothelium and interstitial cells in normal C3H/FeJ mice. In nephritic MRL-lpr and NZB/W kidneys, staining for ICAM-1 is increased in the PT, particularly in the brush border, and is prominent in the glomerular mesangium and the endothelium of large vessels. By Western blot analysis, ICAM-1 is not detected in the urine of normal BALB/c and C3H/FeJ or autoimmune MRL-lpr. By Northern blot analysis, nephritic MRL-lpr and NZB/W have a two- to fivefold increase in steady state levels of ICAM-1 transcripts in the kidney as compared with normal or prenephritic mice. This is paralleled by an increase in MHC class II transcripts. In cultured PT cells, ICAM-1 is expressed at basal levels in PT and is increased by the cytokines interferon-gamma, IL-1 alpha, and TNF-alpha. Thus cytokine-mediated upregulation of ICAM-1 in lupus nephritis may promote interaction of immune cells with renal tissue. The predominant apical expression of ICAM-1 opposite to the basolateral Ia expression suggests a novel role for this adhesion molecule in PT.

Animals↗
PubMed1989

Molecular cloning and characterization of a novel murine T cell surface antigen, YE1/48.

YE1/48 is a murine cell surface disulphide-linked dimeric Ag consisting of two 45,000-50,000 Mr subunits. It is expressed on some T lymphoma lines at high levels but its expression on normal lymphocytes is very low. The functional significance of this Ag is currently unknown. We have now cloned a cDNA encoding the YE1/48. Sequence analysis revealed that it encodes a Type II membrane protein of 262 amino acids (30,500 MW), with 44 amino acids in the N-terminal cytoplasmic domain, 22 amino acids in the transmembrane domain and 196 amino acids in the C-terminal extracellular domain. There are three potential N-linked glycosylation sites in the extracellular domain all of which are probably used in the mature protein. No significant homology can be identified with other known protein sequences in the data base or with human CD28(T44), a human T cell activation antigen consisting of two 44,000 Mr subunits. The protein sequence includes in its extracellular domain the arginine-glycine-aspartic acid tripeptide, a potential cell-adhesive binding site, and a sequence similar to the consensus domain of any metal-binding proteins. However, whether these sequences are functional is unknown. Genomic Southern analysis of C57BL/6, BALB/c and C3H mice has demonstrated a restriction fragment length polymorphism. The analysis has also strongly suggested the existence of some other genes with sequences highly homologous to the YE1/48 gene. The YE1/48 gene appears to be expressed at very low levels in a wide range of lymphoid cells with no restriction to their differentiation stages. Interestingly, YE1/48 expression appears to be induced in pre-B cells after transformation by Abelson virus, suggesting an association of YE1/48 expression with the transformation of T and pre-B Cells.

Amino Acid Sequence↗
PubMed1989

MALA-2, mouse homologue of human adhesion molecule ICAM-1 (CD54).

In humans, lymphocyte adhesion to cells is mediated by the protein heterodimer CD11a/CD18 (Leu-CAMa, LFA-1) and its ligand CD54 (ICAM-1). Although the murine CD11a/CD18 is well characterized, the mouse homologue of human ICAM-1 has not been identified. In the present study a rat monoclonal antibody to the murine lymphocyte activation antigen MALA-2 was found to inhibit in a dose-dependent manner the phorbol ester-enhanced aggregation of mouse lymphoblasts, an adhesion-specific assay, and hence to define an adhesion molecule. By immunofluorescence flow cytometry the antigen expression was low on spleen cells but it largely increased after stimulation with mitogens. The antigen was expressed by some, but not all, lymphoid cell lines, and myelomonocytic and mastocytoma cells were also positive. In frozen tissue sections MALA-2 was mainly detected on germinal center B cells, dendritic cells, macrophages and vascular endothelium, including high endothelial venules. Cell surface labeling followed by immunoprecipitation and gel electrophoresis indicated that the antigen is a sialoglycoprotein which has a relative molecular mass of 95 kDa and displays a faster electrophoretic mobility under non-reducing conditions. The function, cellular distribution and molecular properties of MALA-2 are indistinguishable from those of human ICAM-1.

Animals↗
PubMed1989

Molecular cloning of murine intercellular adhesion molecule (ICAM-1).

We have previously reported a murine lymphocyte surface antigen MALA-2 of approximately 95,000 Mr which is expressed mainly on activated lymphocytes. The rat monoclonal antibody YN1/1 that detects this antigen profoundly inhibits mixed lymphocyte response. We have now purified MALA-2 and determined its partial amino acid sequence. By using non-redundant synthetic oligonucleotides as probes, based on the amino acid sequence, we have isolated two full length cDNA clones encoding MALA-2. The two clones are identical except for the 5' end sequence. Expression of MALA-2 on transfected COS cells is only achieved with one of the two cDNA clones. The nucleotide sequence as well as the deduced amino acid sequence of MALA-2 display striking homology with those of the recently reported human intercellular adhesion molecule ICAM-1. All the unique features of the human ICAM-1, including its homology with the neural adhesion molecule NCAM, its internal repeat structure and the immunoglobulin-like structure, are found in MALA-2. Furthermore, purified MALA-2 crosslinked to a solid support binds Con A blasts that express LFA-1, the putative receptor for ICAM-1, and the binding can be blocked by YN1/1 antibody or antimurine LFA-1 antibody indicating a direct interaction of these molecules in cell adhesion. Therefore, we consider MALA-2 to be the murine homolog of human ICAM-1. Since ICAM-1 is known to be of primary importance in immune responses and inflammatory reactions, having a monoclonal antibody and a mouse model will provide the opportunity to study the functional role of ICAM-1 in vivo.

Amino Acid Sequence↗
PubMed1988

IL-2 and IL-4 stimulate different subpopulations of double-negative thymocytes.

Double-negative (CD4-/CD8-) thymocytes from young adult mice can be separated into two distinct subpopulations on the basis of the binding of mAb 7D4 directed against the receptor for IL-2. The 7D4+ cells have predominantly nonrearranged TCR beta-chain genes and express incomplete 1.0-kb beta-messages, whereas the 7D4- cells have rearranged beta-genes and express complete 1.3-kb as well as incomplete 1.0-kb beta-messages. These two populations of double-negative thymocytes also differ in their responses to IL-2 and IL-4. The 7D4+ cells are nonresponsive to IL-2 alone or IL-2 plus PMA but they are stimulated to proliferate by the combination of IL-4 and PMA. In contrast, the 7D4- cells vigorously proliferate in response to IL-2 alone or IL-2 plus PMA but they respond poorly to IL-4 alone or IL-4 plus PMA. These results suggest that IL-2 and IL-4 may be involved in the stimulation of immature thymocytes at distinct steps of their differentiation. IL-4 together with PMA stimulate immature thymocytes which seem to express the IL-2R but do not respond to IL-2.

Animals↗