Biomedical subjects

A Yachie

Publications and source records attributed to A Yachie.

At least 73 records · Page 4Linked to original sources

PubMed1994

Efficient induction of immunoglobulin production in neonatal naive B cells by memory CD4+ T cell subset expressing homing receptor L-selectin.

The humoral response in newborns is mainly restricted to IgM production, which may be attributable to the naive nature of both B and T cells at birth. In light of the current evidence that memory (CD45RO+) CD4+ T cells help B cell differentiation, the present study was undertaken to examine whether a specified population within memory CD4+ T cells could induce the maturation of neonatal naive B cells. In the conventional PWM-stimulated cultures, the generation of IgG- and IgA-producing cells in addition to IgM production by neonatal B cells was significantly enhanced by co-cultures with memory, but not naive, CD4+ T cells. Memory CD4+ T cells were further divided into two populations based on expression of homing receptor L-selectin. These memory CD4+ T cell subpopulations appeared to behave in different fashions concerning help for Ig production by naive (sIgD+) and mature (sIgD-) B cells. L-selectin-negative memory CD4+ T cells exhibited helper function for Ig secretion by mature B cells. Intriguingly, Ig production by neonatal B cells as well as adult naive B cells, although less than that by mature B cells, was efficiently promoted by L-selectin-positive memory CD4+ T cells rather than L-selectin-negative ones. The results suggest that the capability of neonatal naive B cells to secrete IgG and IgA can be elicited by appropriate T-cell signals, especially from the L-selectin-positive population within memory CD4+ T cells, seemingly indicating its possible role for isotype switching in B cells.

Adult↗

PubMed1994

Ionizing radiation induces apoptotic cell death in human TcR-gamma/delta+ T and natural killer cells without detectable p53 protein.

The p53 tumor suppressor gene has been shown to be involved in programmed cell death, apoptosis, in murine immature thymocytes after treatment with ionizing radiation. Ionizing radiation also induces apoptosis in peripheral mature lymphocytes. In this work, we investigated the p53 participation in radiation-induced apoptosis in human peripheral blood lymphocytes (PBL) subpopulations. Exposure to gamma-irradiation resulted in an appreciable induction of apoptotic cell death in TcR-alpha/beta+ (CD4+ and CD8+) T cells, TcR-gamma/delta+ T cells, B cells and natural killer (NK) cells, as assessed by DNA fragmentation as well as the morphological characteristics. Importantly, it was found that there was a marked difference among PBL subpopulations as regards the induction of p53 protein by gamma-irradiation. Similar to previous observations for murine thymocytes, p53 induction in TcR-alpha/beta+ T cells and B cells after gamma-irradiation was evident by Western blot analysis. Radiation-induced apoptosis in TcR-alpha/beta+ T cells and B cells was efficiently inhibited by cycloheximide, indicating the requirement of de novo protein synthesis, including p53 protein, for radiation-induced apoptosis in both subpopulations. In marked contrast, no identifiable levels of p53 protein were induced in either TcR-gamma/delta+ T or NK cells after gamma-irradiation. In addition, it was demonstrated that radiation-induced cell death in TcR-gamma/delta+ T and NK cells could be prevented by interleukin-2, but not by cycloheximide. These results imply that radiation-induced lymphocytic apoptosis can be mediated by p53-dependent or -independent mechanisms.

Adult↗

PubMed1994

Mature helper T cell requirement for immunoglobulin production by neonatal native B cells injected intraperitoneally into severe combined immunodeficient (SCID) mice.

It is accepted that human neonatal naive B cells produce mainly IgM in vivo as well as in vitro. Our previous work has demonstrated that i.p. injection of neonatal B cells together with adult mature T cells induces substantial levels of human IgG in the serum of SCID recipient mice. The present study was further attempted to determine the cellular components required for immunoglobulin production by neonatal B cells in SCID mice. When neonatal B and adult T cells were transferred into the SCID mice, human immunoglobulins, largely of IgG, were maximally detected in the serum around 6 weeks after a cell transfer. Depletion of CD4+ T cells from adult T cells resulted in undetectable levels of human immunoglobulin in the serum. By contrast, CD4+ T cell-enriched populations exhibited an enhancing effect on immunoglobulin production by neonatal B cells. Higher levels of immunoglobulin, including IgA and IgM, were detected in the peritoneal fluid than in the serum as early as 2 weeks after the cell transfer. Human T cells expressing activation antigens such as CD45RO and HLA-DR antigens were identified in the peritoneal lavages. These results suggest that neonatal naive B cells are able to differentiate into cells producing all classes of immunoglobulin in the presence of mature CD4+ T cells in a SCID mouse environment. The peritoneal cavity of SCID mice appears to provide a suitable place for immune responses by human cells, possibly in association with a certain xenogeneic reaction.

Adult↗

PubMed1994

Kawasaki disease with a concomitant primary Epstein-Barr virus infection.

A two year old boy exhibited not only clinical manifestations which suggested a recurrence of Kawasaki disease (KD) but also evidence of a primary infection by Epstein-Barr virus (EBV) including tonsillitis, splenomegaly and atypical lymphocytosis in the peripheral blood. An inverted CD4/CD8 ratio in lymphocyte subsets suggested the presence of infectious mononucleosis (IM). Epstein-Barr virus titers (viral capsid antigen-immunoglobulin G 1:20; Epstein-Barr virus-associated nuclear antigen < 1:10) showed an acute EBV infection and the presence of EBV genome in the blood was determined by the polymerase chain reaction technique. In Japan, the peak incidence of KD and IM is in children under 4 years of age. From the investigation of EBV titers, it has been reported that some patients with KD develop an associated, unusual primary EBV infection. Kawasaki disease concurrent with a primary EBV infection as in this case, suggests the possibility of an etiologic agent related to the KD rather than to the EBV infection itself.

Child, Preschool↗

PubMed1994

The relationship between serum levels of interleukin-6 and thyroid hormone in children with acute respiratory infection.

To determine whether monocyte-derived humoral factors such as tumor necrosis factor-alpha (TNF alpha), interleukin-1 beta (IL-1 beta), and IL-6 modulate serum thyroid hormone levels in infectious disorders, we measured serum levels of these monocyte-derived products, T3, T4, and C-reactive protein (CRP) in 59 out-patients with acute respiratory infection, aged 5 months to 15 yr (mean +/- SD, 5.7 +/- 4.2 yr). To minimize individual variation in their clinical and nutritional conditions, we selected out-patients with fever lasting for at least 3 days who had no severe disturbance of food intake. Serum T3 concentrations tended to be low in these subjects; 3 (5.1%) had levels below 1.2 nmol/L, L, and 13 (22.0%) had levels below 1.5 nmol/L. Serum T3 levels in 22 patients with elevated IL-6 (> 15 pg/mL) were significantly lower than those in 19 patients with normal IL-6 (< or = 5 pg/mL; T3, 1.7 +/- 0.4 vs. 2.2 +/- 0.6 nmol/L; P < 0.05). The serum IL-6 concentration was correlated inversely with the serum T3 level (r = -0.324; P = 0.012) as well as the T3/T4 ratio (r = -0.279; P = 0.032). Furthermore, a significant negative correlation was observed between CRP (induced mainly by IL-6) and T3 (r = -0.408; P = 0.001) or the T3/T4 ratio (r = 0.302; P = 0.020). On the other hand, TNF alpha was measurable in only 9 of 59 patients, and there was no correlation between TNF alpha and levels of thyroid hormone, CRP, or IL-6. Serum IL-1 beta was weakly detected in only 1 patient. On follow-up study of 10 of these patients, the serum T3 and T3/T4 ratio increased significantly with a reciprocal decrease in IL-6 and CRP during convalescence. No remarkable change in the serum T4 level was observed in our study. Our data suggest that the euthyroid sick syndrome is relatively common in children with acute respiratory infection, and IL-6 appears to mediate this syndrome in infectious disorders.

Acute Disease↗

PubMed1993

Absence of bcl-2 expression by activated CD45RO+ T lymphocytes in acute infectious mononucleosis supporting their susceptibility to programmed cell death.

bcl-2 proto-oncogene encodes an inner mitochondrial membrane protein that blocks programmed cell death (apoptosis). There is now increasing evidence that regulation of bcl-2 expression is a determinant of life or death in normal lymphocytes. We have recently described that activated (CD45RO+) CD4+ and CD8+ T cells in acute infectious mononucleosis (IM) undergo apoptotic cell death on culturing, indicating an activation-driven cell death of mature T cells. In this work, we examine bcl-2 expression by activated T cells in acute IM using a flow-cytometric analysis with an anti-bcl-2 monoclonal antibody (MoAb). It was consistently observed that most T cells from acute IM patients displayed only much less bcl-2, while normal T cells expressed bcl-2 relatively strongly. Multicolor analysis showed that bcl-2-lacking T cells in acute IM were restricted to the CD45RO+ (activated) populations of CD4+, as well as CD8+ T cells. In contrast, the relatively intense levels of bcl-2 were expressed in both CD45RO+ and CD45RO- T-cell populations from normal subjects. This marked difference in bcl-2 expression of CD45RO+ T cells between acute IM and normal controls was also confirmed by Western blot analysis. Activated (CD45RO+) T cells with low bcl-2 expression, but not bcl-2-expressing CD45RO- T cells, in acute IM patients were found to die easily when cultured without added growth factors. However, in normal individuals, both CD45RO+ and CD45RO- T cells were relatively stable on culturing. These findings suggest that lack of bcl-2 expression by activated (CD45RO+) T cells in acute IM might be associated with their susceptibility to programmed cell death.

Adolescent↗

PubMed1993

A novel T cell activation antigen identified by monoclonal IMN3.1 antibody and expressed preferentially on human T cells susceptible to apoptotic cell death.

When cultured without appropriate growth factors, most of activated (CD45RO+) T cells expanded in acute EBV-induced infectious mononucleosis (IM) easily die via an apoptotic cell death mechanism, indicating one Ag-driven selection in the periphery. In this work, we attempted to raise the mAb against cell surface molecules, preferentially expressed on T cells entering apoptosis, by immunizing PBMC from an acute IM patient. We obtained one mAb, termed IMN3.1, that could define clearly the expansion of activated (CD45RO+) T cells in the blood of acute IM patients. In contrast to its intense expression on IM T cells, the IMN3.1-reactive Ag was only dimly expressed on CD45RO+ (memory or previously activated) populations of T cells from normal individuals. Although naive (CD45RO-) populations of T cells usually lacked IMN3.1 Ag, this Ag was inducible relatively late after in vitro activation of naive T cells. The cellular distribution and molecular characterization of IMN3.1-reactive Ag suggested that IMN3.1 mAb appeared to recognize a novel activation-associated cell surface determinant of about 120 kDa m.w., which might be predominantly expressed on apoptosis-prone T cell lineage cells, such as IM T cells, thymocytes, cytokine-dependent T cell lines, and anti-Fas-sensitive T cell lines.

Adult↗

PubMed1993

Increased levels of urinary interleukin-6 in Kawasaki disease.

Kawasaki disease (KD) often presents with abnormal urinary findings, such as aseptic pyuria, mild proteinuria and microscopic haematuria. In this study, we measured urinary interleukin-6 (IL-6) by a sensitive sandwich ELISA assay using mouse monoclonal antibodies against recombinant IL-6 to elucidate the role of IL-6 in the pathogenesis of renal lesions in KD. Serum IL-6 levels were increased in acute KD as well as in febrile controls. Importantly, urinary IL-6 levels were consistently elevated in patients with acute KD, but much lower in febrile controls. Urinary IL-6 levels returned steadily to normal during the convalescent phase. In addition to IL-6, urinary levels of N-acetyl-beta-D-glucosaminidase (NAG) and beta 2-microglobulin (beta 2-mg) were also elevated during the acute phase of this disease. Eosinophils and macrophages were identifiable in urinary sediments from these patients. The increased levels of urinary IL-6 in combination with increased NAG and beta 2-mg seemed to suggest the presence of certain renal parenchymal lesions with cellular infiltration during the acute phase of the disease. IL-6 may serve as clinically useful parameter for the detection and monitoring of the renal involvement in KD.

Acetylglucosaminidase↗

PubMed1993

Increased plasma endothelin levels in Kawasaki disease: a possible marker for Kawasaki disease.

Plasma immunoreactive endothelin (iET) levels were investigated in patients with Kawasaki disease (KD). The iET level was 2.49 +/- 0.13 pg/mL in KD patients and 1.32 +/- 0.06 in age-matched control subjects, showing a significant increase with KD. The iET level was not increased in patients with febrile inflammatory diseases of bacterial origin without KD (non-KD group). Parameters indicating an inflammatory reaction, such as C-reactive protein, platelet count, white blood cell count, and interleukin-6 level, were increased in the KD patients. However, they were similarly increased in the patients with febrile diseases of bacterial origin and showed no significant differences between the two groups. This study is the first to report that plasma iET levels are elevated in a disease mainly involving vasculitis. These results suggest that blood iET levels are increased in KD patients as a result of the associated vascular endothelial damage and that iET can be a useful marker for the diagnosis of KD.

Biomarkers↗

PubMed1993

[Expression of surface CD11b antigen and eosinophil activation].

Recent evidences suggest that the expression of adhesion molecules on eosinophils and endothelial surface play pivotal roles in the migration of activated eosinophils to the site of allergic inflammation. Among these, CD11b/ICAM-1 system is known to be responsible for at least part of the eosinophil/endothelial adhesion. CD11b expression on the surface of circulating eosinophils is significantly elevated in various allergic disorders, including atopic dermatitis and bronchial asthma. Various eosinophilopoietic cytokines, including IL-3, IL-5 and GM-CSF induced rapid upregulation of CD11b expression on eosinophils in vitro. These observations suggest that surface CD11b may serve as a useful parameter of eosinophil activation and may reflect the in vivo level of eosinophilopoietic cytokines.

Cell Adhesion Molecules↗

PubMed1992

Differential expression of apoptosis-related Fas antigen on lymphocyte subpopulations in human peripheral blood.

The Fas Ag is a newly defined cell-surface molecule that may mediate apoptosis. The antibody against Fas Ag can induce the apoptotic cell death in cell lines expressing this Ag. PBL subpopulations at various ages were here examined for Fas expression by two-or three-color flow-cytometric analyses using anti-Fas mAb. It was found that Fas Ag was appreciably detected on a proportion of T and B cells, whereas its expression was absent for NK cells. For CD4+ and CD8+ T cells, Fas Ag was expressed preferentially on CD45RO+ (memory or previously activated) populations, but not on CD45RO- naive ones. TCR-gamma/delta+ T cells, especially their CD45RO+ subsets, also expressed Fas Ag. Expectably, neonatal T cell subpopulations, most of which had the naive (CD45RO-) phenotype, expressed little Fas Ag. Fas-expressing B cells dominated in surface(s) IgD- populations, but neonatal B cells as well as adult sIgD+ B cells had little Fas Ag. The Fas Ag was inducible after in vitro mitogenic stimulation of naive T and B cells from neonatal blood. These observations suggested that expression of Fas Ag on T and B cells in the peripheral blood might reflect their in vivo Ag-activated status. In contrast to Fas-expressing cultured cell lines, however, viability of in vitro stimulated T and B cells as well as freshly isolated CD45RO+ T cells was not significantly changed after the treatment with anti-Fas mAb, indicating that additional cellular conditions to Fas expression might be required for anti-Fas-induced cell death.

Antigens, Surface↗

PubMed1992

Defective production of interleukin-6 in very small premature infants in response to bacterial pathogens.

In the present study, a whole-blood culture was employed to examine the ability of preterm and term newborn infants to produce interleukin-6 (IL-6) in response to major bacterial pathogens such as group B streptococci, Escherichia coli, Listeria monocytogenes, and Streptococcus pneumoniae. Similarly, in response to stimulation with lipopolysaccharide, a potent stimulant for monocyte cytokine production, appreciable levels of IL-6 activity in the stimulated whole blood from term newborns as well as adults was effectively induced by all of these pathogens. In contrast to that of term infants, the bacteria-induced IL-6 production of preterm infants, especially those born before 30 weeks of gestation, was somewhat decreased (P less than 0.01 for each pathogen). It was also demonstrated that IL-6 responses to lipopolysaccharide stimulation were reduced in preterm newborns (for term versus preterm newborns less than 30 weeks of gestation, P was less than 0.01). These findings imply some inherent abnormality of monocytes in preterm babies. The diminished IL-6 production may be partly responsible for the susceptibility of preterm newborn infants to bacterial infections.

Adult↗

PubMed1992

Detection and clinical usefulness of urinary interleukin-6 in the diseases of the kidney and the urinary tract.

Interleukin-6 (IL-6) plays a key role in inflammatory and immune responses in the host. In the present study, the IL-6 activity in urine from patients with various renal diseases was examined to elucidate the pathological and clinical significance of urinary IL-6. In patients with mesangial proliferative glomerulonephritis (mes-PGN) including, IgA nephropathy, the urinary IL-6 activity tended to increase with the progression of mesangial hypercellularity. In four patients with IgA nephropathy, urinary IL-6 activity increased markedly but transiently during episodes of acute exacerbation associated with upper respiratory tract infection. In addition, it was demonstrated that urine from patients with other types of PGN such as poststreptococcal acute glomerulonephritis and membrano-proliferative glomerulonephritis contained large quantities of IL-6. However, the levels of urinary IL-6 activity were almost within the normal range in non-proliferative glomerular diseases such as membranous nephropathy, minimal change nephrotic syndrome and lupus nephritis (WHO class I and V), non-glomerular bleeding and orthostatic proteinuria. It should be noted that a marked increase in urinary IL-6 was often observed in the patients with urinary tract infection. These results indicated that IL-6 in urine might be derived from various types of cells participating in inflammatory reactions not only in the renal parenchyma but also in the urinary tract.

Adult↗

PubMed1991

A novel subpopulation of CD45RA+ CD4+ T cells expressing IL-2 receptor alpha-chain (CD25) and having a functionally transitional nature into memory cells.

Differential expression of various isoforms of leukocyte common antigen (CD45), which arises from alternate mRNA splicing, identifies naive and memory populations of human T cells. Some memory (CD45RO+ CD45RA-) populations of CD4+ T cells from adult individuals express IL-2 receptor (IL-2R) alpha-chain (CD25), but naive (CD45RO- CD45RA+) CD4+ T cells only do so to a small degree. We found that a small but significant fraction of CD4+ T cells in neonatal blood expressed CD25, although most generally exhibited the phenotype of naive cells. It was demonstrated that purified neonatal CD25+ CD4+ T cells expressed mRNA for the IL-2R alpha-chain. Two-color immunofluorescence analysis disclosed that a CD25+ population of neonatal CD4+ T cells had the naive (CD45RA+ CD45RO-) phenotypes. These CD25+ CD4+ T cells from newborns could express mRNA for some specified lymphokines such as IL-4, IL-5, and interferon-gamma on activation in a similar manner to CD45RO+ (memory) CD4+ T cells from adults. Notably, polymerase chain reaction analysis demonstrated that neonatal CD45RA+ CD4+ T cells expressing CD25 contained spliced mRNA transcripts possibly encoding CD45RO in addition to CD45RA-associated transcripts, seemingly indicating that this population might be in the recently antigen-primed states. Such a small population of CD45RA+ CD4+ T cells expressing CD25 appeared to be present in the blood throughout human life. The results suggest that CD4+ T cells with the naive (CD45RA+) phenotype expressing IL-2R alpha-chain (CD25) represent the novel transitional population in the maturation process of naive into memory CD4+ T cells.

Adult↗

PubMed1991

Expression of CD45R0 (UCHL1) by CD4+ and CD8+ T cells as a sign of in vivo activation in infectious mononucleosis.

CD45R0 (UCHL1), a member of leucocyte common antigen family, is expressed largely on previously activated or memory T cells. We examined CD45R0 expression of T cell subpopulations in patients with Epstein-Barr virus (EBV) induced infectious mononucleosis (IMN) as a sign of in vivo activation. Consistent with the notion that activated CD8+ T cells expand in acute IMN; the majority of CD8+ T cells in patients with acute IMN expressed CD45R0 to the similar extent to HLA-DR expression. Most CD4+ T cells in these patients also demonstrated marked expression of CD45R0 as well as HLA-DR antigens, compared with age-matched controls. Expression of CD45R0 by CD4+ T cells in patients with acute IMN was more notable than their HLA-DR expression. While predominant CD8+ T cells resulted in decreased percentages of CD4+ T cells, CD4+ T cells expressing CD45R0 were shown to be significantly elevated in absolute number. The results suggest that both CD4+ and CD8+ T cells may be activated by stimulation with EBV infection. The appearance of two T cell subpopulations expressing CD45R0 in acute IMN implies their immunoregulatory roles in the control of EBV-infected cells.

Antigens, CD↗

PubMed1991

Preferential expression of IL-2 receptor subunits on memory populations within CD4+ and CD8+ T cells.

Using anti-Tac and anti-Mik-beta 1 monoclonal antibodies to alpha and beta subunits of the interleukin-2 receptor (IL-2R), respectively, a marked difference in expression of IL-2R subunits on blood CD4+ and CD8+ T cells was demonstrated between adults and newborns. In the adult blood, reciprocal expression of IL-2R alpha and IL-2R beta was observed in CD4+ and CD8+ T cells. Some CD4+ T cells expressing IL-2R alpha were often detected, but IL-2R beta + CD4+ cells were very few. On the other hand, CD8+ T cells expressed significant IL-2R beta but little IL-2R alpha. In marked contrast to adult individuals, both CD4+ and CD8+ T cells from the newborns, which seemed to consist mainly of naive populations, showed only negligible expression of IL-2R subunits. It was found that IL-2R subunits appeared to be preferentially expressed on CD4+ and CD8+ T cells with memory phenotypes in the adult blood. Isolated memory (CD45RO+) CD4+ and CD8+ T cells, unlike naive (CD45RO-) ones, were able to proliferate in response to exogenous IL-2 as well as the recall antigen. The present results suggest that IL-2R subunits expressed on circulating T-cell subsets may play an important role in memory T-cell function.

Adult↗

PubMed1990

Role of interleukin 6 for differential responsiveness of naive and memory CD4+ T cells in CD2-mediated activation.

The present study was undertaken to elucidate different requirements for CD2-mediated activation of naive (CD45RO-) and memory (CD45RO+) CD4+ T cells. A mitogenic combination of anti-CD2 (anti-T11(2) and anti-T11(3] mAbs could effectively induce the proliferation of memory CD4+ T cells even in the absence of monocytes. In marked contrast, naive CD4+ T cells did not disclose any proliferative responses to anti-CD2 mAbs, when monocytes were absent in culture. This differential responsiveness of naive and memory CD4+ T cells appeared to be related largely to a difference in IL-6-producing ability between both populations. IL-6 among monocyte-derived cytokines could correct unresponsiveness of naive CD4+ T cells to anti-CD2 stimulation. Unlike naive CD4+ T cells, memory CD4+ T cells produced IL-6 by themselves, with its mRNA being expressed on anti-CD2 stimulation. Anti-IL-6R mAb significantly inhibited proliferation of memory CD4+ T cells seen in the anti-CD2-stimulated cultures without monocytes, indicating the involvement of their own production of IL-6 in CD2-mediated activation. The results suggest an essential role of IL-6 for triggering of CD4+ T cells via the CD2 molecule.

Adult↗

PubMed1990

Differential expression of CD45RO (UCHL1) and its functional relevance in two subpopulations of circulating TCR-gamma/delta+ lymphocytes.

We examined the developmental profile of TCR-gamma/delta+ cells with respect to CD45RO expression. Although total TCR-gamma/delta+ cells were negligible in the neonatal blood and increased with advancing age, most blood TCR-gamma/delta+ cells markedly expressed CD45RO without a distinction of age, probably reflecting a different CD45RO expression of two subsets defined by BB3 and delta TCS1 mAbs. The vast majority of BB3+ cells expressed CD45RO, whereas expression of CD45RO was virtually absent in the delta TCS1+ population. Functional studies revealed that, while both TCR-gamma/delta+ cell subsets showed CD3-mediated activation, only BB3+ (or Ti gamma A+) cells, but not delta TCS1+ cells, appeared to proliferate in response to PPD in PPD-reactive individuals. The results suggested that the CD45RO+ (BB3+ or Ti gamma A+) subset among blood TCR-gamma/delta+ cells may be mainly involved in the memory or primed component of the immune system responding to some foreign antigens.

Adolescent↗