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Biomedical subjects

G Del Prete

Publications and source records attributed to G Del Prete.

At least 73 records · Page 4Linked to original sources
PubMed1989

Role of interleukins in induction and regulation of human IgE synthesis.

Studies of human IgE synthesis are summarized and provide further insight into the cellular and molecular mechanisms involved in IgE regulation, as well as in the alterations responsible for IgE disregulation in some pathological conditions. These include the demonstration that IL-4 is the essential factor for the induction of human IgE syntheses. Another T cell-derived lymphokine, IFN-gamma negatively regulated the IgE synthesis induced by IL-4. These two lymphokines can be produced by different T helper cells, as shown in mice, but they can also be the product of the same T cells clones. Additional cellular and/or molecular signals appear to be involved in the IL-4-induced IgE synthesis, but their precise role in this process is undetermined. Finally, alternations of one or more of these regulatory mechanisms can be detected in patients with pathological conditions characterized by hyperproduction of IgE. In particular, the increased prevalence of T cells clones able to produce IL-4 appears to be a distinctive feature of patients with common atopy whereas a reduction in the proportion of IFN-gamma-producing T cells seems to be peculiar of both patients with hyper-IgE syndrome and patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Defective in vitro production of gamma-interferon and tumor necrosis factor-alpha by circulating T cells from patients with the hyper-immunoglobulin E syndrome.

Circulating T cells from four patients with the hyper-IgE syndrome were found to produce significantly lower concentrations of interferon-gamma (IFN-gamma) in response to stimulation with phytohemagglutinin (PHA) than did T cells from eight age-matched healthy controls, three patients with atopic dermatitis and one patient with chronic granulomatous disease. A clonal analysis revealed that patients with hyper-IgE syndrome had markedly lower proportions of circulating T cells able to produce IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) in comparison with controls. In contrast, the proportions of peripheral blood T cells able to produce IL-4 or IL-2 were not significantly different in patients and controls. All the four patients with hyper-IgE syndrome showed high proportions of circulating CD4+ helper T cells able to induce IgE synthesis in allogeneic B cells, as well. Such an activity for IgE synthesis appeared to be positively correlated with IL-4 production by T cells and inversely related to the ability of the same T cells to produce IFN-gamma. Since IFN-gamma exerts an inhibitory effect on the synthesis of IgE and both IFN-gamma and TNF-alpha play an important role in inflammatory reactions, we suggest that the defective production of IFN-gamma may be responsible for hyperproduction of IgE and the combined defect of IFN-gamma and TNF-alpha may contribute to the undue susceptibility to infections seen in patients with hyper-IgE syndrome.

Adolescent↗
PubMed1988

IL-4 is an essential factor for the IgE synthesis induced in vitro by human T cell clones and their supernatants.

The property of 109 CD4+ T cell clones (TCC) to induce IgE synthesis in vitro in human B cells was compared with their ability to produce IL-2, IL-4, and IFN-gamma in their supernatants (SUP) after 24-h stimulation with PHA. A significant positive correlation was found between the property of TCC to induce or enhance spontaneous IgE synthesis and their ability to release IL-4. In contrast, there was an inverse relationship between the IgE helper activity of TCC and their ability to release IFN-gamma, whereas no statistical correlation between the property to induce IgE synthesis and to produce IL-2 was observed. The ability of PHA-SUP from 71 CD4+ TCC to induce IgE synthesis in B cells was also investigated. Twenty-nine SUP (all derived from TCC active on IgE synthesis) induced production of substantial amounts of IgE in target B cells. There was a correlation between the amount of IgE synthesized by B cells in response to these SUP and their IL-4 content. An even higher correlation was found between the IgE synthesis induced by these SUP and the ratio between the amount of IL-4 and IFN-gamma present in the same SUP. Like IL-4-containing SUP, rIL-4 also showed the ability to induce IgE production in B cells from both atopic and nonatopic donors. The addition to B cell cultures of anti-IL-4 antibody virtually abolished not only the IgE synthesis induced by rIL-4, but also that stimulated by TCC and their SUP. In contrast, the IgG synthesis induced by TCC SUP was not or only slightly inhibited by the anti-IL-4 antibody. These data indicate that IL-4 is an essential mediator for the IgE synthesis induced in vitro by human TCC and their SUP in the absence of a polyclonal activator, whereas IFN-gamma seems to exert a negative regulatory effect on the production of IgE.

Adult↗
PubMed1988

Profiles of lymphokine activities and helper function for IgE in human T cell clones.

A large panel of phytohemagglutinin (PHA)-induced T cell clones (690 in total), established from four different human lymphoid tissues (peripheral blood, tonsils, lymph nodes and spleens) by a high-efficiency cloning technique, was characterized according to their pattern of lymphokine production. The majority of both CD4+ and CD8+ clones from all lymphoid tissues produced interleukin (IL) 2 and/or interferon (IFN)-gamma in response to 24-h stimulation with PHA. In contrast, higher proportions of IL 4-producing clones were found among CD4+ clones from tonsils and spleens than from peripheral blood and lymph nodes, whereas only a minority of CD8+ clones from all lymphoid tissues were found to produce IL 4. It was not possible to divide the CD4+ (helper/inducer) clones on the basis of their pattern of lymphokine activity into two clear-cut groups analogous to Th1 and Th2 helper clones described in mice. Although 21 out of 503 (4%) CD4+ T cell clones produced IL 4, but not IFN-gamma or IL 2, and 208 (41%) produced IL 2 and/or IFN-gamma, but not IL 4, a total number of 185 (37%) CD4+ clones showed the ability to produce IL 4 plus IL 2 and/or IFN-gamma. All types of CD4+ T cells (as classified according to their pattern of lymphokine activity) provided help for IgG production in allogeneic B cells. In contrast, helper function for IgE was detectable only among the IL 4-producing clones.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Activation through CD3 molecule leads a number of human T cell clones to induce IgE synthesis in vitro by B cells from allergic and nonallergic individuals.

Seventy-eight clones established from tonsillar T lymphocytes of two nonallergic children were tested under different experimental conditions for their ability to induce in vitro IgE synthesis by B cells from allergic or nonallergic donors. After 24 hr preactivation with phytohemagglutinin (PHA), 11 out of 32 CD4+ clones from the first and 17 out of 36 CD4+ clones from the second tonsil donor showed the ability to induce IgE synthesis in vitro by B cells from both allergic and nonallergic individuals, whereas none of 10 CD8+ clones nor T blasts of PHA-induced cell lines obtained from unfractionated T cell suspensions of the same tonsils had such an effect. Seven of the 11 T cell clones from the first tonsil donor active on IgE production after pre-activation with PHA also induced IgE synthesis in vitro by nonallergic and allergic B cells upon stimulation with anti-CD3 monoclonal antibody. Under the same experimental conditions, virtually all of the T cell clones able to induce IgE synthesis in vitro by target B cells showed the ability to stimulate IgG and IgM production as well. T cell clones were also established from the peripheral blood of a nonallergic donor and were tested for their ability to induce IgE synthesis in autologous B cells. After preactivation with PHA, seven out of 35 CD4+ clones induced the production of detectable amounts of both IgE and IgG in autologous B cells. The addition to the cultures of PHA-stimulated unfractionated T cells inhibited in a dose-dependent manner the IgE but not the IgG synthesis induced by an autologous helper T cell clone in autologous B cells. Taken together, these data indicate that a remarkable proportion of human T cell clones upon triggering of the CD3 molecular complex were able to provide help for the synthesis of IgE in B cells from both allergic and nonallergic individuals. The successful induction of IgE synthesis by single T cell clones was apparently related to the lack of concomitant suppressor activity to which IgE-producing cells appeared to be exquisitely sensitive.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Frequent T4-positive cells with cytolytic activity in spleens of patients with Hodgkin's disease (a clonal analysis).

Purified T lymphocytes isolated from spleens of untreated patients with Hodgkin's disease (HD) were cloned by using a microculture system previously shown to allow clonal expansion of virtually all peripheral blood T lymphocytes. Cells were plated under limiting conditions with irradiated feeder cells and PHA. Interleukin 2 (IL 2)-containing supernatants were added 48 hr later. The phenotypic and functional characteristics of a total number of 221 clones derived from six different HD spleens were investigated and compared with those of 133 clones obtained from three spleens of otherwise healthy individuals who underwent posttraumatic splenectomy. The majority of T cell clones derived from HD spleens expressed the T4+ (helper/inducer) phenotype. However, further functional characterization showed that as much as 50% of these T4+ clones displayed cytolytic activity in a lectin-dependent lytic assay allowing detection of cytolytic cells of any specificity. In contrast, less than 10% T4+ clones derived from control spleens were cytolytic, as assessed by the same lectin-dependent lytic assay. The cytolytic potential of T4+ and T8+ clones established from spleens of patients with HD did not reflect the induction of lymphokine-activated killer cells, because only a minority of them displayed natural killer (NK) activity against NK-sensitive K562 and MOLT-4 cell lines. These findings indicate that T lymphocytes found in the spleens of patients with HD may represent, at least in part, the expansion of a subset present in small percentages among normal peripheral blood or spleen T lymphocytes, which is involved in a cytotoxic reaction.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Human T cell clones can induce in vitro IgE synthesis in normal B cells regardless of alloantigen recognition or specificity for peculiar antigens.

A total number of 119 (98 CD 4+ and 21 CD 8+) T cell clones were established from tonsil and peripheral blood of three nonallergic individuals and examined for their ability to induce in vitro IgE synthesis in normal B cells. Following preactivation for 24 h with phytohemagglutinin, 34 clones (33 CD 4+ and 1 CD 8+) induced normal B cells to synthesize remarkable amounts of IgE in vitro. In contrast, equal numbers of T blasts of phytohemagglutinin-induced T cell lines obtained from unfractionated T lymphocyte suspensions of the same donors did not show such an effect. The in vitro IgE synthesis evoked by T cell clones was detectable between day 6 and 9 and peaked on day 12. Most clones maintained their ability to stimulate in vitro IgE synthesis in repeated assays over a 3-month period. The induction of IgE synthesis by cloned T cells did not reflect alloantigen recognition on target B cells, since T cell clones induced IgE synthesis in B cells from all randomly selected donors tested, including autologous B cells. Preincubation for 24 h with optimal stimulatory concentrations of anti-CD 3 (OKT 3) monoclonal antibody or its addition through the entire culture period also enabled T cell clones to stimulate de novo IgE synthesis in vitro in normal B cells. Virtually all the T cell clones active on IgE synthesis induced the in vitro production of remarkable amounts of IgM and IgG as well. These data indicate that several human T cell clones can induce normal B cells to synthesize immunoglobulin of different classes, including IgE, regardless of alloantigen recognition on target B cells or specificity for peculiar antigens. The activity of these clones was apparently mediated by triggering of the monomorphic molecular complex CD 3, immediately before or during the incubation of T cell clones with the target B cells.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Direct induction of human B-cell differentiation by recombinant interleukin-2.

Recombinant interleukin-2 (rIL-2) induced highly purified human tonsillar B cells to differentiate into immunoglobulin (Ig)-producing cells in vitro. The B-cell response was not due to rIL-2-contaminating substances, but reflected the activity of IL-2 itself, since it was inhibited by addition to the cultures of anti-TAC monoclonal antibody. The rIL-2-induced B-cell response was apparently not mediated by factors released by residual T cells present in B-cell suspensions at undetectable levels, since supernatants (SN) from unstimulated autologous T cells cultured at concentrations even much higher than those possibly contaminating B-cell suspensions did not induce any detectable Ig production. In addition, the Ig production by B cells cultured with SN prepared from high numbers of autologous T cells stimulated with rIL-2, as well as from allo-activated or mitogen-stimulated T cells, was of the same magnitude as the Ig production resulting from direct addition of rIL-2 concentrations comparable with those present in the supernatants. After centrifugation on Percoll density gradients, most of the tonsillar B cells responsive to rIL-2 were recovered in the lower density cell fraction containing a number of larger activated B cells. Moreover, B-cell enriched suspensions from peripheral blood (PB) (which usually contains a lower number of in vivo activated B cells than tonsil) showed poor or no response to rIL-2 alone, but displayed significant Ig production when rIL-2 was added to the cultures in the presence of Staphylococcus aureus Cowan I (SAC) bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗
PubMed1985

Synergy of B cell growth factor and interleukin 2 in the proliferation of activated human B cells.

The activity of purified interleukin 2 (IL2), obtained by the recombinant DNA technology, on the proliferative response of human B cells stimulated with low concentrations of anti-mu antibody was investigated. Recombinant IL2 was capable of augmenting the proliferative response of anti-mu-activated B cells and the T cell activation (Tac) antigen was expressed on a substantial proportion of normal B cells stimulated with anti-mu antibody. However, crude supernatants from protein A-stimulated peripheral blood mononuclear cells, which were found to possess both IL2 and B cell growth factor (BCGF) activities, maintained the ability to promote proliferation of anti-mu-activated B cells after depletion of IL2. In addition, supernatants from some T cell clones, apparently free of IL2 activity, displayed strong BCGF activity in the co-stimulation assay with anti-mu antibody. This BCGF activity was found in 25 kDa fractions by gel filtration and it was unaffected by addition to the cultures of anti-Tac antibody, which consistently inhibited the B cell proliferative response promoted by recombinant IL2. The proliferative response of anti-mu-activated B cells to clonal, IL2-free supernatants containing BCGF and recombinant IL2 present together from the beginning of culture was close to the sum of responses to the two stimulants, separately. In addition, the presence of clonal supernatant containing BCGF from the beginning of culture had a synergistic effect in the response of activated B cells to the subsequent addition of IL2, whereas the initial presence of IL2 had no such an effect on the reactivity of anti-mu-stimulated B cells to the late addition of clonal supernatant containing BCGF. The synergistic effect of BCGF in the IL2-promoted B cell proliferation was probably the result of the recruitment of a greater number of IL2-reactive B cells. In fact, the number of Tac-positive cells was significantly higher in 36-h cultures established in the presence of anti-mu antibody plus clonal supernatant containing BCGF than in cultures stimulated with anti-mu antibody alone. Taken together, these data indicate that anti-mu antibody promotes the expression by normal human B cells of distinct receptors for IL2 and a BCGF distinct from IL2. They also suggest that BCGF can exert a synergistic effect in the IL2-promoted proliferation of activated B cells.

Antibodies, Anti-Idiotypic↗
PubMed1981

Surface immunoglobulins are involved in the interaction of protein A with human B cells and in the triggering of B cell proliferation induced by protein A-containing Staphylococcus aureus.

The nature of surface components responsible for the reactivity of a subset of human B cells with staphylococcal protein A (SpA) was studied. The ability of normal non-T cells or non-T cells from patients with chronic lymphocytic leukemia (CLL) to form rosettes with human red blood cells coated with SpA (SpA-HRBC) was strongly inhibited or abolished by incubation with F(ab')2 fragments of antibodies against human immunoglobulin (Ig), whereas the incubation with F(ab')2 fragments of antibodies against a non-Ig cell surface antigen, such as beta 2-microglobulin, had no effect on the SpA-rosetting of human lymphocytes. The role of the reaction between surface Ig (sIg) and SpA in the triggering of the proliferative response induced by Staphylococcus aureus bacteria strain Cowan I (Cowan Staph) on normal or leukemic non-T cells was also investigated. A parallelism was observed between the mitogenic activity on normal human non-T cells of Cowan Staph and F(ab')2 fragments of immunosorbent-purified rabbit antibodies to human mu-chain. On the other hand, monovalent Fab fragments of anti-F(ab')2 or anti-mu chain antibodies were unable to activate human non-T lymphocytes, but usually induced a partial inhibition of the Cowan Staph-induced cell proliferation. Non-T cells from 2 patients with CLL did not respond to either Fab or F(ab')2 fragments of anti-Ig antibodies, but were stimulated to proliferate by Cowan Staph. However, the proliferative response of non-T cells from these patients to Cowan Staph was markedly inhibited or abolished by the addition to the cultures of F(ab')2 fragments of anti-Ig antibodies. Antibody preparations to human F(ab')2 or gamma-chain inhibited the response of IgG-bearing leukemic cells, whereas the Cowan Staph-induced proliferation of IgM-bearing leukemic lymphocytes was inhibited by the addition to the cultures of either anti-F(ab')2 or anti-mu chain antibodies. The proliferative response to Cowan Staph or normal non-T cells was also inhibited by the addition to the cultures of human and guinea pig polyclonal IgG, whereas IgG from other species, such as goat, ox, horse, and rabbit, were poorly or not at all inhibitory. On a molar basis, the F(ab')2 preparation from human IgG was as potent an inhibitor as intact IgG molecules, whereas Fc gamma was much less effective in inhibiting the Cowan Staph-induced cell proliferation. A monoclonal IgM, isolated from the serum of a patient with CLL, whose lymphocytes were able to form rosettes with SpA-HRBC and to proliferate in vitro after stimulation with Cowan Staph, also showed a marked inhibitory activity on the Cowan Staph-induced proliferation or normal non-T cells. These data suggest that an interaction between SpA present on the bacterial cell wall and a structure located in the Fab region of sIg, which is shared by sIgM, sIgG, and perhaps also by sIg of other classes, plays an important role in the triggering of B cell proliferation induced by SpA-containing staphylococci.

Antibodies↗
PubMed1980

Short- and long-term effects of radiation on T-cell subsets in peripheral blood of patients with Hodgkin's disease.

The present study was undertaken to determine the effect of radiotherapy on subpopulations of peripheral blood T cells from patients with Hodgkin's disease. T cell were purified from each specimen, and proportions and absolute numbers of T lymphocytes bearing receptors for the Fc portion of IgG (TG) and for Fc portion of IgM (TM) were enumerated by rosetting T cells with ox red blood cells (ORBC), which had been coated with anti-ORBC rabbit IgG or IgM, respectively. In untreated patients, the percentage of TG cells was significantly increased, and the percentage of TM cells was significantly decreased when compared with control values. In patients examined after radiotherapy, there was a severe depletion of total T lymphocytes. The percent and absolute values of TM cells were also markedly decreased in comparison with those found in either normal controls or untreated patients. In contrast, relative proportions of TG cells were significantly increased in the same treated patients, but the absolute numbers of these cells were essentially unchanged in comparison with those found before radiation therapy. There was a partial and progressive restoration of the number of TM lymphocytes some years after the treatment, but reduced percentages of TM lymphocytes and increased percentages of TG lymphocytes were still found in patients in continuous complete remission for at least five years or more. Similar alterations of the two T-cell subsets were also found in the peripheral blood of a small group of patients treated with radiation for testicular seminoma. These data clearly demonstrate that radiation therapy has a differential effect on identifiable and distinct subsets of cells in the human T-cell class.

Adult↗
PubMed1979

Macromolecular synthesis in mitochondria isolated from different regions of developing rat brain.

DNA, RNA, and protein synthesis in mitochondria isolated from cerebral hemispheres, brain stem, and cerebellum of 10- and 30-day-old rats was measured. Synthesis of different macromolecules was affected by the respective mitochondrial specific inhibitors, showing a good level of purity of mitochondrial preparations. DNA and protein synthesis in 10-day-old rats was about 70% higher than in 30-day-old animals. In contrast, RNA synthesis did not decrease with age in all the regions examined.

Aging↗
PubMed1979

Mitochondrial DNA, RNA, and protein synthesis in different regions of developing rat brain.

In vivo and in vitro (tissue slices) incorporation of labeled precursors into DNA, RNA, and proteins was measured in mitochondria obtained from cerebral hemispheres, cerebellum, and brain stem of rats at different days of postnatal development. To compare the synthesis of macromolecules in mitochondria with that in other subcellular fractions, the incorporation of labeled precursors into DNA, RNA, and proteins extracted from nuclei and into RNA and proteins extracted from microsomes and cytoplasmic soluble fractions was also measured. The results obtained showed that the incorporation of [3H]thymidine into DNA and of [14C]leucine into proteins of nuclei and mitochondria from the various brain regions examined decreased during postnatal development; however, at 30 days of age the specific radioactivity of mitochondrial DNA was higher than that of nuclear DNA. [3H]Uridine incorporation into RNA decreased from 10 to 30 days of age in nuclei while in mitochondria it was quite similar at both ages. This result may be due to a faster turnover of mitochondrial RNA compared to that of mitochondrial DNA and proteins. The results obtained suggest an active biosynthesis of macromolecules in brain mitochondria and might indicate an intense biogenesis of these organelles in rat brain during postnatal development.

Animals↗