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Biomedical subjects

E Jirillo

Publications and source records attributed to E Jirillo.

At least 163 records · Page 9Linked to original sources

Cell-mediated immune response in patients with type IIa, type IIb and type IV primary hyperlipoproteinaemia.

Plasma lipoproteins inhibit immune function. Polymorphonuclear cell (PMN) and monocyte activities, and pokeweed mitogen (PWM)-driven B cell differentiation in patients with type IIa, type IIb and type IV primary hyperlipoproteinaemia were evaluated. Evidence is provided for a selective impairment of these functional capacities in type IIa and type IIb hyperlipoproteinaemic patients, while immune responsiveness is unaffected in type IV primary hyperlipoproteinaemia. The data suggest a specific immune dysfunction in patients with type IIa and type IIb primary hyperlipoproteinaemia.

Adult↗

Pilot study of intravenous administration of the acid-treated Salmonella minnesota R595 (Re) in cancer patients.

The clinical toxicity of acetic acid-treated "Salmonella minnesota" R595 (Re) organisms was evaluated in 24 cancer patients. Bacteria were injected i.v. four times at increasing doses for a total of 6.5 micrograms. This therapeutic regimen was free of major side effects (one patient had fever higher than 38 degrees C and 10 patients complained of pruritus). Furthermore, this bacterial preparation which possesses a more exposed lipid A on its surface, exhibited immunomodulating capacities in that it normalized the inverted T helper/T suppressor ratio and enhanced natural killer activity in tumor patients. The mechanisms of the lower toxicity and immunomodulating activities of these bacteria compared to other lipid A preparations are discussed.

Acetates↗

Regulatory effects mediated by OKT8+ subsets on B cell response in the elderly.

The B cell responsiveness mediated by T cells has been evaluated in 50 aged donors by using a Pokeweed mitogen (PWM)-driven differentiation system. Peripheral blood mononuclear cells (PBMC) from aged donors exhibited a lower plaque-forming cell (PFC) generation in comparison with young donors. Similar results were obtained by using, on a per cell basis, purified T cells supplemented with Non-T lymphocytes. OKT4+ cell addition to Non-T cells enhanced PFC number, even if values were still lower when compared to young donors. Moreover, results similar to those seen with T-supplemented Non-T cell cultures were obtained by mixing Non-T cells with OKT4+ and OKT8+ lymphocytes. Interestingly, when OKT8+ cells were divided into OKT8+M1+ and OKT8+M1-subsets and used in the assay, both cell fractions suppressed B cell response in aged donors, while this effect was mediated by OKT8+M1+ cells only in the young counterpart. Soluble suppressive factors were responsible for the observed activity, since indomethacin supplementation to cultures or overnight incubation of cells before PWM stimulation abrogated the OKT8+M1--mediated suppression. Taken together, these findings suggest an additional alteration of T-B cell relationship in the elderly.

Aged↗

Effects of a synthetic extract (thymopentin) on the immune system of lepromatous leprosy patients.

Twenty three patients with lepromatous leprosy (LL) not in reactional phase and bacteriologically negative were evaluated for their immune status (T cell frequency and interferon gamma production). In six patients with deficits of both immune parameters, a synthetic thymic extract (TP-5) was administered. At the end of the treatment, a full recovery of immune dysfunction was observed. In the light of these results, the efficacy of TP-5 as an immunomodulating agent in LL patients is discussed.

Adjuvants, Immunologic↗

Functional properties of Salmonella minnesota Rb-bound and Rb-unbound cell fractions in elderly donors.

The capacity of Salmonella minnesota R345 (Rb) binding to human peripheral blood lymphocytes allows the recovery of Rb-bound and Rb-unbound cell populations that elicit different functions. Here, we have applied this method to lymphocytes from aged individuals to evaluate the possibility that such an approach could reverse the senescence-related impaired immune responsiveness. In this regard we show that Rb binding augments either spontaneous or T-dependent plaque-forming cell generation in Rb-unbound fraction. By contrast, Rb-bound cells are enriched for lymphocytes releasing several lymphokines. This experimental approach seems to represent a useful tool to elucidate better the age-related alterations of the immune function.

Aged↗

Immunoregulation in aging.

Senescence of the immune system leads to a decline of functional capacities of lymphoid cells. In this regard, evidence has been provided for a reduction of T and B cell-mediated responses. T-B regulation is also affected by the aging process. Since the proportion of lymphocytes is similar to that observed in young donors, either intracellular or extracellular factors may play an important role in the impaired immunoresponsiveness. An intrinsic defect of T or B cells has been in fact postulated. However, soluble suppressive factors or decreased LK production seem to represent the key events involved in the decline of the immune response. Nevertheless, over the past few years emphasis has been given to the increased lymphocyte membrane microviscosity in the elderly [Rivnay et al: Mech Ageing Dev 10: 71-79, 1979]. All together, these findings suggest a multifactorial therapeutic approach for the correction of the impaired immune response in aged individuals.

Aging↗

Lymphocyte-Salmonella interaction: energy dependence and thiol group involvement.

In order to gain better insight into lymphocyte-Salmonella interaction investigation has been carried out on energy-dependence and involvement of thiol groups in this process by using a modified rosette test. Binding frequency, number of bound bacteria/number of binding lymphocytes and the number of bacteria-binding sites/lymphocyte were found to be enhanced by externally added ATP and decreased by both uncouplers and electron transfer chain inhibitors. Treatment of either bacteria or lymphocytes with thiol reagents, such as mersalyl or N-ethyl-maleimide, prevents lymphocyte-Salmonella adherence, thus showing the presence of thiol groups involved in the binding mechanism in both bacteria and cells. Consistently, as a result of mersalyl inhibition, a decrease in the number of bacteria-binding sites/lymphocyte was also found.

Adenosine Triphosphate↗

Relationship between immune system and gram-negative bacteria, binding of Salmonella pullorum-gallinarum to chicken lymphocytes.

Salmonella pullorum-gallinarum binding to chicken lymphocytes has been evaluated in individuals of different age (1-20 wks). Bacterial adherence has been studied on lymphoid cells recovered from thymus, spleen, bursa and peripheral blood. Binding was age-dependent and neuraminidase treatment of lymphoid cells led to an increase of adherence. In addition, by using two monoclonal antibodies, the CT-1, which defines thymocytes and the M-4 which identifies surface IgM and an avian homologue of mammalian IgD on B lymphocytes, distribution of Salmonella pullorum-gallinarum binding to T and B lymphocytes has been analyzed. Results show that either T lymphocytes or B lymphocytes have the capacity to form rosettes with Salmonella. In particular, B cells from bursa and spleen display the highest capacity of adherence to bacteria, this supporting the defence function which has been attributed to bursa of Fabricius.

Animals↗

Inhibition by antibiotics of Rb Salmonella binding to human peripheral blood lymphocytes.

Several lines of evidence point out that Salmonella minnesota R345 (Rb) possesses the capacity to adhere spontaneously to human peripheral blood lymphocytes. The binding is mediated via the lipopolysaccharide moiety of the bacterial outer membrane. In this report, we have evaluated the effects of various antibiotics on bacterial binding. Our data show that trimethoprim/sulphamethoxazole, chloramphenicol and erythromycin significantly decrease Rb binding, while gentamicin and sisomicin are without effect. Antibiotics display their inhibitory effect by acting on peripheral blood lymphocytes likely by competing with lipopolysaccharide for receptor binding capacity on lymphocyte surface.

Anti-Bacterial Agents↗

Relationship between immune system and gram-negative bacteria. Acid-treated Salmonella minnesota R595 (Re) enhances immune responsiveness in patients with gynecologic malignancies.

Nine patients with gynecologic malignancies (six cervix, two endometrium and one ovary) were injected with acid-treated Salmonella minnesota R595 (Re). Patients received a total of four injections (at increasing doses from 0.5 to 3 micrograms) every 2 weeks. All patients, before treatment, had a severe impairment of their immune system either of cell-mediated immunity (leukocyte inhibiting factor activity) or non-specific immunity (polymorphonuclear cell and/or monocyte-mediated phagocytosis and killing). In contrast, the same patients displayed a normal Natural Killer cell frequency in their peripheral blood as evaluated in an agarose-single cell cytotoxic assay. At the end of the immunotherapeutic regimen, all the above immune functions significantly augmented likely via an immunomodulating effect exerted by the lipid A portion of Salmonella minnesota Re which represents the lipopolysaccharide molecule in these bacteria. This suggests a potential role for lipid A in the treatment of cancer-related immunodeficiency.

Cytotoxicity, Immunologic↗

Adherence of Lyme disease spirochetes to rat lymphocytes.

In the present work, the capacity of Lyme disease (LD) Spirochetes to spontaneously adhere to rat lymphocytes has been evaluated. Borrelia organisms adhere to thymus, spleen, Payer's patches and peripheral blood lymphocytes in a higher frequency than that observed with Salmonella minnesota R345 (Rb) used as reference strain. Employing enriched splenic T and B cell populations, Spirochete binding to B lymphocytes is more elevated than that obtained with Salmonella, while similar percentage of T cells forms rosettes with both microorganisms. Taken together, these findings provide evidence for a novel mode of interaction between LD Spirochetes and host immune system.

Animals↗

Phagocytosis of Leishmania infantum promastigotes by monocytes isolated from Leishmania-infected dogs.

Fifteen dogs with generalised leishmaniasis have been evaluated for their monocyte capacity to ingest Leishmania promastigotes. These cells displayed a lower phagocytic ability when compared to monocytes recovered from normal dogs. Moreover, sera from Leishmania-infected dogs caused a remarkable decrease of monocyte phagocytic ability in healthy dogs, whereas sera from healthy dogs could restore monocyte phagocytosis in sick animals. Similar results were seen when Candida albicans was used as stimulant. Interestingly, supernatants from polyethylenglycole (PEG) treated sera from Leishmania-infected dogs did not inhibit monocyte phagocytosis either in the autologous or in the homologous (healthy dogs) system. This suggests a possible role for serum factor(s) in the impairment of phagocytosis in Leishmania infection.

Animals↗

Relationship between immune system and gram-negative bacteria: monocyte chemotaxis induced by supernatants from human peripheral blood OKT8+ lymphocytes stimulated with smooth and rough Salmonella strains.

It has been recently reported that smooth (S) Salmonella typhimurium LT-2 and rough (R) mutants, S. minnesota R345 (Rb) and R595 (Re), spontaneously adhere to human peripheral blood mononuclear cells (PBMC). The binding is confined to T cells and is mediated by the lipopolysaccharide (LPS) moiety of the bacteria outer membrane. In this study, we have investigated the monocyte chemotactic responsiveness induced by supernatants recovered from human PBMC stimulated with either S or R Salmonella strains. All supernatants were able to trigger monocyte chemotaxis, even if to a different degree according to the bacterial strain used. These data were further supported by experiments which showed that stimulation of PBMC by purified homologous LPS led to the release of a chemotactic lymphokine (CLK) for human monocytes. Moreover, this CLK seems to be released by T cells, and in particular OKT8+ cells, since OKT8- PBMC failed to produce CLK.

Antibodies, Monoclonal↗

Quantitative analysis of lymphocyte-Salmonella interaction and effect of lymphocyte irradiation by Helium-Neon laser.

A model system has been developed to quantitatively investigate bacteria-cell interaction using a rough mutant of Salmonella and human peripheral blood lymphocytes. The effect of lymphocyte irradiation by low-power continuous wave Helium-Neon laser has been investigated since laser therapy in wound and decoubitous ulcer healing could involve the lymphoid cell function. Helium-Neon laser irradiation is shown here to enhance the adherence of Salmonella to lymphocytes. In particular, changes in newly defined binding parameters show that laser irradiation increases the frequency of binding-lymphocytes, the affinity of Salmonella for lymphocytes and the number of lymphocyte receptor sites as well.

Binding Sites↗

Impairment of T immunoregulatory activities in the induction of antibody specific response in aged humans.

T helper (Th) and T suppressor (Ts) functions on the induction of specific antibody response have been studied in 80 aged individuals by means of a plaque-forming cell assay. Of the subjects 45.2% exhibited a reduction of Ts activity on Ig production by adding Concanavalin A (Con A) to cultures on day 0, while 35.7% of aged donors showed a decrease of Th functions by supplementation of Con A on day 2. A small number of individuals displayed a combined deficit (Th + Ts). Furthermore, these defects seem to be related to soluble suppressive factors which might adhere to cell surface. In fact, preincubation of peripheral blood mononuclear cells (PBMC) before their addition to cultures and resuspension in fresh medium normalized the immunoregulatory defects. On the other hand, overnight supernatants from old PBMC transferred to young PBMC cultures induced the same deficit observed in the aged cell suspensions. Finally, Zinc chloride supplementation to cultures was able to correct the deficient Th activity only. These data suggest an additional defect of immunoregulation in the elderly.

Adolescent↗

Relationship between immune system and gram-negative bacteria. III. Functional analysis of human peripheral blood lymphocyte subpopulations separated by cytoadherence with Salmonella minnesota Rb.

Spontaneous adherence of bacteria to human peripheral blood mononuclear cells (PBMC) represents a useful tool for analysis of lymphocyte subsets with different functions. We have recently shown that PBMC can be divided into 2 populations based on their ability to bind Salmonella minnesota R345 (Rb) bacteria. By using these procedures, here, we provide evidence that Rb-bound and Rb-unbound PBMC populations give similar proliferative responses to phytohemagglutinin (PHA) and concanavalin A (Con A), while the pokeweed mitogen (PWM)-induced proliferative and differentiative responses are higher in the Rb-unbound than in the Rb-bound PBMC fraction. Moreover, enhanced PWM-induced responses are obtained in Rb-unbound cell cultures enriched for T4+ cells. When B (non-E rosetting) cells are cultured with purified T lymphocytes from the Rb-bound (T-Rb+) and Rb-unbound (T-Rb-) fractions, comparable PWM-induced mitogenic responses are observed. The T-Rb- population contains a higher percentage of cells expressing T4+ phenotype, and when added to B cell cultures a more elevated PWM-induced IgA, IgG and IgM synthesis is observed than in B cell cultures containing T-Rb+ cells. These results suggest that the T-Rb- fraction is enriched for T cells which help IgA, IgG and IgM responses.

B-Lymphocytes↗

Relationship between immune system and gram-negative bacteria. IV. T lymphocytes from Lpsd mice possess binding site(s) for Rb Salmonella.

We have previously shown that Salmonella minnesota R345 (Rb) spontaneously binds to 50 to 55% of human peripheral blood mononuclear cells (PBMC). In the present study, we have compared Rb cytoadherence to lymphoid cells from various tissues of lipopolysaccharide (LPS) hyporesponsive (Lpsd) and LPS responsive (Lpsn) mouse strains. A higher number of spleen cells from Lpsd mice (C3H/HeJ and C57BL/10ScN) bound Rb bacteria (22 to 30%) than cells from Lpsn mice (4 to 9%). Rb bound mainly to T cells, and cytoadherence occurred in both Lyt-1+ and Lyt-2+ T cell subsets. By contrast, purified splenic B cells from Lpsd and Lpsn mice gave less than 4% Rb cytoadherence. In both mouse strains, cytoadherence was mediated by the homologous LPS structure, because purified Rb-LPS blocked Rb Salmonella binding to T cells. On the other hand, smooth Salmonella typhimurium LT-2 LPS (S-LPS) and Salmonella R595 (Re) LPS (Re-LPS), which contain mainly lipid A, were without effect on Rb binding. Increased Rb binding was seen with T cells from Peyer's patches (PP), mesenteric lymph nodes (MLN), and peripheral blood than from spleen of C3H/HeN (Lpsn) mice; however, greater cytoadherence was always seen with T cells of these tissues from C3H/HeJ mice. Interestingly, treatment of whole spleen or purified T cells from C3H/HeN mice with neuraminidase enhanced cytoadherence to levels seen with C3H/HeJ cells. The observed Rb binding to PP, MLN, and PBMC cells in both mouse strains suggests that gut microbial environment may play an important role in Rb cytoadherence. This is also supported by the evidence that when spleen cells of germfree and conventional mice were tested for Rb binding, higher cytoadherence was observed in conventional mice only. Taken together, these results indicate that T cells of Lpsd mice express binding site(s) for Salmonella, whereas Lpsn mice have T cells with these structure(s) in a cryptic configuration.

Adhesiveness↗