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Biomedical subjects

A Velardi

Publications and source records attributed to A Velardi.

At least 73 records · Page 4Linked to original sources
PubMed1986

Functional analysis of cloned germinal center CD4+ cells with natural killer cell-related features. Divergence from typical T helper cells.

Granular lymphocytes co-expressing the Leu-7 (NK-related) and CD4 (T helper cell) markers are selectively localized in the germinal centers of lymphoid tissues. Leu-7+ cells (greater than 98% of which co-expressed CD4) were isolated from inflammatory tonsils and were cloned by the limiting dilution technique. Clones were analyzed for their phenotypic and functional characteristics. CD4+-Leu-7+ cell-derived clones retained their CD3 and CD4 surface antigens, lost the Leu-7 marker, and acquired HLA-DR determinants. In comparison with clones derived from peripheral blood or tonsil CD4+ cells, CD4+-Leu-7+ tonsil cell-derived clones showed similar low frequencies of cytotoxic precursors. In contrast, the frequency of interleukin 2 (IL 2) and B cell growth factor producing clones was much lower for tonsil CD4+-Leu-7+ cells than for CD4+ blood or tonsil progenitors. We conclude that germinal center CD4+-Leu-7+ cells are a subset of T cells unable to produce IL 2 in response to phytohemagglutinin or anti-CD3 stimulation, which is effective on the majority of T helper cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Isolation and characterization of Leu 7+ germinal-center cells with the T helper-cell phenotype and granular lymphocyte morphology.

Leu 7+ cells in germinal centers of lymphoid tissues largely (greater than 90%) coexpress the T helper-cell marker, Leu 3. In this study we have isolated Leu 7+ (Leu 3+) cells from pharyngeal and palatine tonsils and we have analyzed their surface phenotype, morphologic and cytochemical characteristics, and functional properties. All of these features have been compared with those of T helper-cell populations with natural killer (NK)-like characteristics that we have previously described in peripheral blood. Leu 7+ (Leu 3+) cells from tonsil germinal centers display morphological and cytochemical features of granular lymphocytes and express the T3 marker in the absence of Leu 15. Following stimulation with phytohemagglutinin (PHA) or anti-T3, Leu 7+ (Leu 3+) cells express interleukin-2 (IL-2) receptors and proliferate to some extent in response to IL-2. The localization of Leu 7+ (Leu 3+) cells in B-dependent areas of lymphoid tissues suggests that they may play a regulatory role in B-cell proliferation and/or differentiation. Here we show that Leu 7+ (Leu 3+) cells do not produce B-cell growth factor (BCGF) and do not help pokeweed mitogen (PWM)-driven B-cell differentiation. Therefore, Leu 7+ (Leu 3+) germinal-center cells are distinct from "classic" T-helper cells of blood and lymphoid tissues.

Adult↗
PubMed1985

Quantitative and functional analysis of a human lymphocyte subset with the T-helper (Leu 3/T 4+) phenotype and natural killer (NK)-cell characteristics in patients with malignancy.

Approximately 20% of normal blood lymphocytes expressing the T-helper (Leu 3/T 4+) surface phenotype display natural killer (NK)-like features such as cytoplasmic granules and the ability to bind NK-cell targets. In this study, we have assessed the frequency, phenotypic features, and functional capabilities of such cells in a variety of lymphoid malignancies or solid tumors. In each patient group, the percentage of granular lymphocytes within the Leu 3/T 4+ T-helper subset was significantly increased. A large percentage of these cells coexpressed the Leu 7 or Leu 15 marker. When Leu 3+ cells from patients with high proportions of such NK-like cells (or Leu 3+-Leu 15+ cells from selected patients) were isolated with a fluorescence-activated cell sorter, these cells did not proliferate in response to allogeneic cells or T-cell mitogens, nor did they provide help for B-cell differentiation. They also did not suppress T-cell proliferative responses or B-cell differentiation. Freshly prepared Leu 3+ granular lymphocytes did not display NK-cell cytotoxic functions. However, after short-term culture in the presence of phytohemagglutinin (PHA), Leu 3+-Leu 15+ cells expressed T-cell growth factor (TCGF) receptors, had a detectable proliferative response to exogenous TCGF, and acquired the ability to lyse NK-cell targets. These studies demonstrate that, in a variety of malignancies, the lymphocyte subpopulation expressing the T-helper (Leu 3/T 4+) phenotype may be comprised largely of cells with NK-like features and functional capabilities distinct from those of classical helper T cells.

Antibodies, Monoclonal↗
PubMed1985

A large subpopulation of lymphocytes with T helper phenotype (Leu-3/T4+) exhibits the property of binding to NK cell targets and granular lymphocyte morphology.

A discrete subpopulation of lymphocytes sharing several phenotypic characteristics with natural killer (NK) cells was identified within the circulating pool of human lymphocytes that bear the T helper marker Leu-3. This Leu-3+ subpopulation of cells formed cell conjugates with the NK target cell lines K562 and MOLT-4, but did not bind to mouse myeloma and hybridoma cell lines that are insensitive to NK cells. The Leu-3+ lymphocytes binding to NK cell targets contained cytoplasmic granules similar in ultrastructure and cytochemistry to those previously defined in granular lymphocytes with NK function, except that the granules in Leu-3+ cells were smaller and fewer in number. Unlike classical NK cells, however, the granular Leu-3+ cells did not kill the target cells to which they bound, even after treatment with interferon. The proportion of granular Leu-3+ cells with the capacity to bind to NK cell targets was approximately 7% at birth and increased to approximately 21% of the Leu-3+ cells in adults. These observations suggest the possibility of a lineal relationship between the granular Leu-3+ cells and granular Leu-3- cells with NK capability.

Acid Phosphatase↗
PubMed1985

Expression of NK-lineage markers on peripheral blood lymphocytes with T-helper (Leu3+/T4+) phenotype in B cell chronic lymphocytic leukemia.

Heterogeneity within lymphocyte subsets expressing T-helper (T4+/Leu3+) or T-suppressor (T8+/Leu2+) markers was analyzed in 38 patients with B cell chronic lymphocytic leukemia (B-CLL) and in 11 age-matched controls. Co-expression of NK-lineage markers (M1, Leu7) on Leu2+ or Leu3+ cells was investigated by two-color immunofluorescence, and the proportion of granular lymphocytes within each subset was determined by cytochemical staining for acid phosphatase. B-CLL patients and normal controls had similar absolute numbers of cells per microL with T-suppressor phenotype. However, the proportion of Leu2+ cells co-expressing the Leu7 antigen was higher in the B-CLL patients than in the control subjects (54 +/- 3% v 27 +/- 4%, P less than .0001). The absolute number per microL of cells with T-helper phenotype was somewhat decreased in B-CLL patients compared with normal subjects (649 +/- 104 v 799 +/- 33, P less than .02), with a consequent decrease of the helper/suppressor ratio. Furthermore, co-expression of the Leu7 and, more strikingly, of the M1 markers was increased significantly on Leu3+ cells from B-CLL patients compared with normal controls (11 +/- 2% v 2 +/- 0.7%, P less than .002 for Leu7 and 40 +/- 5% v 4 +/- 1%, P less than .00001 for M1). Cytochemical studies showed that a large proportion of Leu3+ cells from B-CLL patients were granular lymphocytes, as suggested by the co-expression of natural killer (NK) cell markers. The emergence of a population of Leu3+ granular lymphocytes with NK markers, which is barely detectable in normal subjects, may provide an explanation for the impairment of T cell functions repeatedly described in B-CLL.

Adult↗
PubMed1985

Expression of the Chediak-Higashi lysosomal abnormality in human peripheral blood lymphocyte subpopulations.

Fusion of lysosomes to form a giant cytoplasmic inclusion is a major abnormality expressed by multiple hematopoietic and non-hematopoietic cell types in Chediak-Higashi (C-H) patients. In this study, the extent of involvement of lymphoid cell subpopulations was defined. Purified populations of B cells, natural killer (NK) cells, and helper T cells were obtained from two C-H patients and normal controls by immunofluorescence staining of their blood mononuclear cells with the monoclonal antibodies HB-2, Leu-7, or Leu-3 followed by fluorescence-activated cell sorting. Cytochemical and ultrastructural analyses as well as functional assays were performed to determine whether or not the C-H lysosomal abnormality was expressed in the different lymphocyte subpopulations. B cells expressed the C-H defect following activation and differentiation. All of the Leu-7+ cells and a significant proportion of the Leu-3+ cells displayed the C-H abnormality. These Leu-3+ cells share the NK lineage characteristics of granular lymphocyte morphology and the capacity to bind to NK cell targets. In contrast, the C-H abnormality was not observed in non-NK target-binding cells with T helper phenotype, in which clusters of lysosomes formed a normal Gall body. Moreover, T cell functions were unimpaired in C-H patients. These observations raise the issue of the lineal relationship between granular and nongranular lymphocytes typed as T cells on the basis of cell surface antigen markers.

Adult↗
PubMed1985

Postnatal liver hemopoiesis in mice: generation of pre-B cells, granulocytes, and erythrocytes in discrete colonies.

Morphologic analysis of hemopoietic tissue in mouse liver reveals the persistence of erythropoietic, granulopoietic, and lymphopoietic activity for approximately 2 wk after birth. Near the end of the first postnatal week, we noted a remarkable reorganization of the hemopoietic cells that was characterized by a transition from a diffuse distribution of mixed erythroid, myeloid, and lymphoid elements to a focal pattern of discrete hemopoietic colonies scattered among the cords of hepatic parenchymal cells. Each hemopoietic focus contained cells progressing along a single differentiation pathway (i.e., erythroid, myeloid, or lymphoid cells). Megakaryocytes were seen as solitary cells surrounded by hepatocytes. This pattern of colonization was observed in all strains of mice examined. In the livers of mice with known hemopoietic defects, however, differences were found in the duration of postnatal hemopoiesis. Accessory cells with macrophage-like features were consistently observed in erythropoietic foci, but were rarely seen in lymphoid foci. The latter were formed by pre-B cells identifiable by the presence of cytoplasmic mu-heavy chains and the absence of light chain expression. The occurrence of discrete colonies of erythroid, myeloid, and pre-B lymphoid cells in the postnatal liver suggests that each is derived from a single, committed precursor cell. This anatomical compartmentalization according to cell type offers a useful model system for analysis of hemopoietic differentiation and of the generation of clonal diversity among B lineage cells.

Animals↗
PubMed1984

Monoclonal antibody-defined T-cell phenotypes and phytohemagglutinin reactivity of E-rosette-forming circulating lymphocytes from untreated chronic myelocytic leukemia patients.

T-cell phenotypes, as defined by murine monoclonal antibodies, (OKT3, OKT4, OKT8, OKIa1), and phytohemagglutinin (PHA) reactivity, were evaluated in E-rosette forming cells (T-cells) from 10 untreated chronic myelocytic leukemia patients. The proportion of T4+ cells was lower in patients than in controls (41.6 versus 61.7%, P less than 0.02); whereas the proportion of T8+ cells was similar in patients and controls. The decrease in T4+ cells in CML resulted in a decrease in circulating T4+/T8+ ratio (P less than 0.02). The Ia1+ T-cells were increased in most CML (8 of 9) patients, while control subjects never displayed Ia1+ T-lymphocytes (P less than 0.01). The PHA reactivity of E-rosette forming lymphocytes was significantly impaired in CML patients with respect to controls (P less than 0.02). The presence of Ia antigen on T-cells was positively correlated with the T8+ cell phenotype (P less than 0.001) and inversely correlated with the T4+ (helper) cell phenotype (P less than 0.05). Furthermore, there was a trend towards an inverse correlation between the PHA response and the level of Ia1+ or T8+ cells, there is no correlation between PHA reactivity and T4+ phenotype. The results suggest that the T-lymphocyte population from untreated CML patients is intrinsically abnormal.

Adult↗
PubMed1984

A mature thymocyte-like phenotypic pattern on human cord circulating T-lymphoid cells.

Cord blood samples from healthy full-term newborns were tested with antimature and antiimmature lymphoid-cell monoclonal antibodies, as well as more traditional markers, in order to identify the phenotype of circulating precursor cells. The results demonstrated that human cord blood contains a lower number of OKT3+, E-rosetting mature T cells than adult blood, very high levels of OKT10+ cells, and few OKT9+, OKT8+ OKT3-, and OKT4+ OKT3- cells. Although the finding of OKT9+ and OKT10+ cord circulating cells could be indicative of cell activation, double marker studies in newborn blood pointed to phenotypically immature lymphoid subsets at different stages of maturation, according to Reinherz's hypothesis. In addition, the absence of nuclear Tdt-positive and hot-rosetting cells, together with the fact that most of these are OKT3+, OKT10+, OKT4+, or OKT8+ cells, suggests that the surface phenotype of newborn lymphocytes is similar to that of mature thymocytes.

Antibodies, Monoclonal↗
PubMed1984

Lymphocyte surface antigens: a longitudinal study during the first month of human life.

A longitudinal study on human T lymphoid surface antigens was performed on blood samples from 6 infants during their first month of life. Although the results indicate a sudden increase in the percentage of OKT3+ and E-RF+ cell types a few hours after birth and a less rapid decrease of OKT6+ and OKT9+ circulating cells, high levels of OKT10+ cells persisted. This finding suggests that infant blood contains immature phenotypic T lymphocytes after birth.

Age Factors↗
PubMed1984

An immunofluorescence analysis of the ontogeny of myeloid, T, and B lineage cells in mouse hemopoietic tissues.

The population dynamics of granulopoietic cells, B-lineage cells, and T lymphocytes were analyzed by immunofluorescence in mouse hemopoietic tissues as a function of age. Mac-1+ myeloid cells were present on day 11 of gestation in the liver, where they peaked shortly after birth and declined subsequently. Waves of myeloid population growth began in spleen and bone marrow by days 15 and 19, respectively. Mac-1+ cells increased in number to relatively low plateau levels in spleen by the 3rd wk after birth, whereas in the bone marrow higher plateau levels were reached around 3 mo of age. The 14.8 monoclonal antibody was utilized as one marker of B-lineage precursor cells. 14.8+ cells were detected in the liver on day 11 of gestation, reached peak numbers during the first week after birth and decreased thereafter. On day 15 and 19, 14.8+ cells were found in spleen and bone marrow, respectively, and progressively increased in numbers to reach plateau levels in both sites by 3 mo of age. Mu+ pre-B cells appeared in significant numbers in the 13-day fetal liver, reached a peak shortly after birth, and disappeared from the liver by the end of the second postnatal week. Pre-B cells were found in the spleen and bone marrow on days 15 and 19, respectively. In the spleen pre-B cells reached peak values at birth and disappeared 2 wk later. In spite of the sequential appearance of mu+ pre-B cells in fetal liver, spleen, and bone marrow, their sIgM+ B cell progeny appeared in all these hemopoietic tissues on day 17 of gestation. In the liver, sIgM+ B cells reached their peak at birth and declined thereafter. In the spleen and bone marrow, B cells increased to plateau levels between 1 and 4 mo of age. Thy-1.2+ T cells were relatively late acquisitions in all three hemopoietic tissues. Finally, the expression of the 14.8 antigen by mu+ cells was examined as a function of gestational age. While pre-B cells from day-13 fetuses had no detectable 14.8 antigen, the antigen was weakly expressed on the vast majority of the mu+ pre-B cells by day 17 of gestation. Newborn liver cells expressing 14.8 antigen were found to include a small proportion of cells with peroxidase+ granules. Thus, demonstration of rearrangement and expression of immunoglobulin genes may be required for precise identification of cells of B lineage early in ontogeny.

Animals↗
PubMed1984

Analysis of the reactivity of four anti-mouse IgM allotype antibodies with mu+ B lineage cells at various stages of differentiation.

We have used two rat monoclonal antibodies (Mab) (Bet-1 and 331.12), a mouse Mab (AF6-78.25), and an alloantiserum (SJA anti-BAB/14) in two-color immunofluorescence analysis and enzyme-linked immunosorbent assays to examine the expression of IgM allotypes at various stages of mouse B cell development, especially at the pre-B cell stage. In agreement with findings previously reported by others, these antibodies displayed the patterns of allotypic reactivity with IgM+ B cells and plasma cells from the appropriate strains of mice: Bet-1 antibody is specific for a allotype, AF6-78.25 and SJA anti-BAB/14 for b allotype, and 331.12 for both a and b allotypes but not e allotype. These antibodies, however, did not react with isolated mu-heavy chains prepared from secreted molecules or synthesized in situ by normal pre-B cells or pre-B cell-derived hybridomas. The requirement of light chain participation in the expression of IgM allotypic determinant(s) was additionally suggested by analysis of a fetal liver-derived hybridoma (F1-26-11) that has been shown to secrete IgM heteromolecules composed of C57BL/6-derived mu-chain and BALB/c-derived kappa-chains. In contrast to the nonreactivity with C57BL/6 mu-only pre-B cell-derived hybridomas, all three antibodies with specificity for the b allotype (AF6-78.25, SJA anti-BAB/14, and 331.12) reacted with this particular hybridoma. After treating surface IgM molecules on B lymphocytes with papain to cleave Fab fragments, the b allotype reactivity of AF6-78.25 mouse Mab, but not 331.12 rat Mab, disappeared, whereas the a allotype reactivities of two rat Mab (Bet-1, 331.12) were not altered. These results suggest that the IgM allotypic epitopes defined by these antibodies appear to be sterically dependent on the assembly of the whole IgM molecules, and rat Mab 331.12 and mouse Mab AF6-78.25 define two separate b allotype specificities, one on the Fc portion and the other on the Fab portion of the IgM molecules, respectively.

Animals↗
PubMed1983

The in vivo effect of thymic factor (thymostimulin) administration on circulating immune complexes and serum lysozyme levels in untreated Hodgkin's disease patients.

The in vivo effect of a calf thymus extract, thymostimulin, on the levels of circulating immune complexes (CIC) and serum lysozyme was evaluated in 32 patients with untreated Hodgkin's disease. Using the platelet aggregation test for detecting CICs, 12 patients (37%) had positive titers before thymostimulin treatment; 3 patients (10%) remained positive following therapy. Serum levels of Clq-binding immune complexes were evaluated (greater than 24.5 micrograms/ml) in 8 patients prior to thymostimulin therapy (mean value: 42.3 micrograms/ml); 3 patients continued to have elevated levels after treatment. Serum lysozyme levels for Hodgkin's patients was similar to control values (10.6 vs. 8.3 micrograms/ml); however, the Hodgkin's patients with initially elevated CICs had a lower serum lysozyme level than patients with initially normal CICs (12.9 vs. 7.3, p less than 0.02). Thymostimulin increased serum lysozyme levels in the Hodgkin's patients in whom the CICs were initially elevated (7.3 vs. 10.4 micrograms/ml, p less than 0.05). These data suggest that thymostimulin exerts an effect on the nonspecific immune system of Hodgkin's disease patients.

Animals↗
PubMed1983

The in vivo effect of thymic factor (thymostimulin) administration in Hodgkin's disease patients. Correlation of skin reactivity and leukocyte migration-inhibition factor in the sera of anergic subjects.

The correlation between leukocyte migration-inhibition and delayed skin hypersensitivity was studied in the sera of 15 anergic untreated Hodgkin's disease patients before and after administration of thymostimulin. Skin tests, negative in all patients before treatment, turned positive in 9 after thymostimulin. Prior to treatment, 10 patients had normal and 5 enhanced migration; none was leukocyte migration-inhibition factor (LIF) positive (mean 1.14 +/- 0.30). Seven of the 9 patients (77.9%) whose skin tests became positive, 3 of whom had an initially enhanced migration, were LIF positive after thymostimulin. LIF closely paralleled skin hypersensitivity both before and after thymostimulin. It is suggested that thymostimulin evokes the differentiation of a lymphocyte subpopulation(s) responsible for both factors investigated.

Cell Migration Inhibition↗
PubMed1983

Circulating immune complexes and serum lysozyme levels in untreated Hodgkin's disease. Their relationship to immune function.

Complement-fixing and non-complement-fixing circulating immune complexes were determined in 42 previously untreated Hodgkin's disease patients by Pl.A.T., C1qB-ELISA and KgB tests. The functional status of the monocyte-macrophage system was evaluated by measuring the serum lysozyme levels. These parameters were then correlated with the patient's immunocompetence, as assessed by the percentage of E-rosette forming cells and the PHA response. The Pl.A.T. was positive in 35.7% patients, the KgB-test in 34.3% and the C1qB-ELISA in 19%. There was overlapping of positive results in 37.5% patients. No correlation was found between CIC levels and stage, unfavourable histology or B symptoms. The PHA response was significantly depressed in CIC + patients, as detected by the C1qB-ELISA technique (p less than 0.0025). The data on serum lysozyme offer an insight into the possible mechanism regulating serum levels of CICs in Hodgkin's disease. Two distinct situations seem to exist: in the first, high CIC levels are associated with normal or low serum lysozyme values (p versus normal controls: n.s.); in the second, serum lysozyme levels are high and CIC absent (p less than 0.005 versus control values). The lowest lysozyme levels are also associated with a depressed lymphocyte PHA response. It could, therefore, be concluded that, in Hodgkin's disease, the presence, or absence, of CICs is directly correlated to the degree of monocyte-macrophage clearance activity and that the host's immunocompetence plays an important role in the induction and/or maintenance of this functional defect.

Antigen-Antibody Complex↗
PubMed1982

The in vivo effect of a thymic factor (thymostimulin) on immunologic parameters of patients with untreated Hodgkin's disease.

The in vivo effect of a calf thymus extract (thymostimulin, TS) on the E-rosetting capacity, PHA blastogenic response, serum migration inhibitory activity (LIF) and skin reactivity to recall antigens was evaluated in 19 untreated patients with Hodgkin's disease. In patients the mean percentage of peripheral blood lymphocytes forming E-rosettes increased from 47 to 55.7% (P less than or equal to 0.001; normal: 58.9). The mean PHA stimulation index rose with all three concentrations tested but did not reach normal values. Serum LIF was positive in only one patient prior to treatment with a mean LIF for all patients of 0.75 (P less than or equal to 0.005). Skin tests were positive in ten patients (52.6%) prior to therapy and 18 patients following therapy (94.7%; P less than or equal to 0.05). Thymostimulin, in vivo, appears to return immunologic competency to a population of untreated patients with Hodgkin's disease.

Adult↗