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E Cenci

Publications and source records attributed to E Cenci.

At least 19 recordsLinked to original sources
PubMed1992

Antigen-specific cytolysis of infected cells in murine candidiasis.

Immune L3T4+ and Lyt-2+ lymphocytes play an important role in the acquired resistance of mice to challenge with virulent Candida albicans, and release macrophage-activating cytokines in response to yeast cells in vitro. To determine whether antigen (Ag)-specific cytotoxic T lymphocytes are generated during fungal infection, purified L3T4+ and Lyt-2+ lymphocytes from immunized mice were cultured in the presence of syngeneic accessory cells, Candida Ag, and IL-2. Yeast-infected bone marrow macrophages and peritoneal exudate neutrophils were used as target cells in a standard 51Cr release assay. Ag-specific, MHC-unrestricted lysis of infected macrophages was evident with immune Lyt-2+ cells after 5-10 days in culture. Under the same experimental conditions, the cytotoxic activity of L3T4+ cells was negligible, but its expression could be induced by the addition of anti-CD3 antibody. Culturing immune Lyt-2+ cells for shorter periods of time (1-2 days) resulted in preferential lysis of infected neutrophils. In addition, at limiting effector cell numbers, Ag-specific MHC-restricted lymphocytes with cytotoxic activity to infected macrophages could be identified. We suggest that C. albicans infection stimulates multiple cytotoxic T-cell precursors with varying recognition stringency, which may have an important role in antifungal resistance in vivo.

Animals↗
PubMed1992

Course of primary candidiasis in T cell-depleted mice infected with attenuated variant cells.

Anti-CD4, anti-CD8, or anti-interferon-gamma (IFN-gamma) antibodies or combinations of them were administered in the early stages of chronic infection of mice with a Candida albicans live vaccine strain, and the animals were monitored for course of primary infection, development of delayed-type hypersensitivity, resistance to reinfection, production of interleukin 2 (IL-2) and IFN-gamma in vitro by splenic lymphocytes, and levels of IL-2 and IFN-gamma transcripts in these cells. CD4+ cell and IFN-gamma depletion resulted in the development of fatal candidiasis by the attenuated yeast vaccine. In contrast, either treatment alone modified the course but not the outcome of primary infection, though each prevented the development of resistance to reinfection. Our data thus indicate that both IFN-gamma and CD4+ cells participate in resistance to primary infection with attenuated yeast cells and are critical in the induction of persistent systemic anticandidal immunity.

Animals↗
PubMed1992

Effect of corticosteroid treatment on interleukin-1 and tumour necrosis factor secretion by monocytes from subjects with asthma.

Peripheral blood monocytes (PBM) may be activated in asthmatic patients, a condition usually reverted by corticosteroid (CS) treatment. In the present research we have evaluated the spontaneous or lipopolysaccharide (LPS)-induced production of interleukin 1 (IL-1) and tumour necrosis factor (TNF) by PBM obtained from 14 asthmatic subjects during an asthmatic attack and after 1 week of CS treatment. The control group included 20 healthy volunteers. PBM obtained during severe asthma showed a pattern of IL-1 and TNF secretion similar to that of normal subjects. After CS treatment, IL-1 levels did not change significantly in comparison to baseline values, while LPS-induced TNF production was apparently related to the degree of airway obstruction after CS treatment. In fact, TNF production by PBM from CS-responsive subjects was significantly decreased in comparison to the levels determined before CS treatment, while PBM from CS-resistant subjects produced the same cytokine levels regardless of CS treatment. The present study suggests that the determination of LPS-induced TNF secretion by PBM could be used to confirm the effectiveness of CS treatment in asthma.

Adrenal Cortex Hormones↗
PubMed1992

Gamma interferon modifies CD4+ subset expression in murine candidiasis.

A single injection of monoclonal antibody to gamma interferon administered in conjunction with a live Candida albicans yeast cell vaccine resulted in the detection of nonprotective Th2 rather than protective Th1 responses and altered the early expression of interleukin 4 and gamma interferon mRNA in CD4+ cells.

Animals↗
PubMed1991

Candida albicans-specific Ly-2+ lymphocytes with cytolytic activity.

To determine whether antigen (Ag)-specific cytotoxic T lymphocytes are generated during experimental Candida albicans infection, purified L3T4+ and Ly-2+ lymphocytes from immunized mice were cultured in the presence of syngeneic accessory cells, C. albicans Ag, and interleukin 2. Yeast-infected bone marrow macrophages were used as target cells in a standard 51Cr-release assay. Freshly isolated L3T4+ and Ly-2+ lymphocytes failed to lyse either target cell type. However, Ag-specific, major histocompatibility complex (MHC)-unrestricted lysis of infected macrophages was evident with immune Ly-2+ cells after 7-10 days in culture. The cultured cells were greater than 98% Thy-1+, CD3+, L3T4-, Ly-2+, T cell receptor alpha/beta + T cells, and their lytic activity was potentiated by the addition of anti-CD3 monoclonal antibodies. At limiting effector cell numbers, Ag-specific MHC-restricted lymphocytes with cytotoxic activity against infected macrophages could be identified. We suggest that C. albicans infection stimulates multiple cytotoxic cell precursors with varying recognition stringency, which include MHC class I-restricted, Ag-specific cytotoxic T lymphocytes.

Animals↗
PubMed1991

Macrophage colony-stimulating factor in murine candidiasis: serum and tissue levels during infection and protective effect of exogenous administration.

Serum and tissue concentrations of the macrophage-specific colony-stimulating factor (CSF-1) and the number of CSF-1-responsive cells in bone marrow were investigated in mice chronically infected with a low-virulence strain of the opportunistic zoopathogenic yeast Candida albicans. CSF-1 levels in serum, brain, kidney, liver, and lung were significantly increased shortly after infection and remained elevated during the 2 weeks preceding the onset of specific T cell-dependent immunity. The number of monocytic precursor cells was also increased in the bone marrow of infected mice. When macrophages from naive donors were exposed in vitro to purified murine CSF-1, their anticandidal activity in vitro appeared to be enhanced. CSF-1 was also administered in vivo to prospective recipients of a lethal C. albicans challenge. The results showed that the factor could effectively potentiate the animals' resistance to the yeast, as shown by increased survival times and reduced recovery of viable C. albicans from the organs of the CSF-1-treated mice. Therefore, the present data suggest that CSF-1 is likely to contribute to early resistance to fungal infection and could be successfully exploited in experimental models of antifungal immunotherapy.

Animals↗
PubMed1991

Defective candidacidal activity of alveolar macrophages and peripheral blood monocytes from patients with chronic obstructive pulmonary disease.

We investigated the in vitro candidacidal activity of alveolar macrophages (AM) and peripheral blood monocytes (PBM) from normal subjects or from patients with chronic obstructive pulmonary disease (COPD) displaying defective skin test delayed-type hypersensitivity (DTH) reactivity to seven antigens including Candida albicans. The results showed that cells from patients with COPD were significantly less effective than cells from control subjects in the killing of C. albicans. To explore whether the observed functional impairment could be reversed, interferon-gamma (IFN-gamma) was added to AM and PBM from patients with COPD, alone or in the presence of lipopolysaccharide (LPS) as a suboptimal stimulus. The cells were cultured for 24 h and then assayed for anti-Candida activity. After IFN-gamma treatment, the fungicidal activity of cells from patients with COPD was comparable to that of unstimulated AM or PBM from healthy donors. Treatment with IFN-gamma plus LPS resulted in a further enhancement in the killing of C. albicans. To gain more insight into the mechanisms involved in the modulation of killing, we evaluated the possible stimulating activity of IFN-gamma plus LPS treatment on the secretion of tumor necrosis factor (TNF) and interleukin-1 (IL-1), two cytokines produced by activated macrophages and capable of stimulating natural effectors. The results showed that IFN-gamma plus LPS can indeed stimulate TNF and IL-1 secretion by AM and PBM from patients with COPD. Therefore, a precise role can reasonably be ascribed to these soluble factors in the observed augmentation of candidacidal activity as ascertained by treatment with IFN-gamma plus LPS.

Aged↗
PubMed1990

T-cell subsets, IFN-gamma production and efferent specificity in anti-parental tumor immunity induced by mouse sensitization with xenogenized variant cells.

In addition to previous evidence for a role of L3T4+ T cells in the protective anti-parental tumor immunity induced by xenogenized variant cells of a murine lymphoma (L5178Y/DTIC), we have investigated the possible participation in this effect of L5178Y tumor-specific lymphocytes of the Lyt-2+ T cell subset. Spleen cells from L5178Y/DTIC tumor-immunized mice produced high levels of IFN-gamma in vitro in response to parental antigens, and this activity was only abolished by treating the responder population with anti-Thy-1.2 antibody or a combination of anti-L3T4 and anti-Lyt-2.2 monoclonal antibodies (MAbs) plus complement. Positively selected L3T4+ and Lyt-2+ cells also produced IFN-gamma in vitro, provided accessory cells (plastic-adherent and Thy-1- Ia- splenocytes, respectively) were added to the lymphocyte-tumor cell cocultures. The production of IFN-gamma by purified L3T4+ and Lyt-2+ cells was inhibited by addition of the respective anti-class-II and anti-class-I H-2 antibody to the cultures. Administration of anti-IFN-gamma MAb in vivo significantly impaired the resistance of L5178Y/DTIC-immune mice to challenge with parental cells, as manifested by survival criteria and increased tumor-cell proliferation in the spleens of antibody-treated mice. Although anti-parental tumor protection in vivo and T-cell activation in vitro for IFN-gamma production were strictly antigen-specific, bystander tumor inhibition was observed when antigenically irrelevant cells were inoculated with the L5178Y lymphoma. These results suggest that both L3T4+ and Lyt-2+ T cells play a role in the protective anti-parental tumor immunity induced by xenogenized cells, and that their activity may involve IFN-gamma-mediated stimulation of non-specific tumoricidal mechanisms.

Animals↗
PubMed1990

T cell subsets and IFN-gamma production in resistance to systemic candidosis in immunized mice.

In addition to previous evidence for the roles of T cell-dependent immunity and delayed-type hypersensitivity in acquired resistance to systemic candidosis in mice, in the present study we have investigated the relative contributions of L3T4+ and Lyt-2+ lymphocytes in the protective immunity induced by vaccination with low virulence Candida albicans cells. We have also addressed the issue of the mode of Candida Ag recognition by specific T cells leading to cytokine release. Spleen cells from immunized mice produced high levels of IFN-gamma in vitro in response to Candida Ag, and this activity was abolished only by the combined treatment of the responder population with anti-L3T4 and anti-Lyt-2.2 mAb plus C. Positively selected L3T4+ and Lyt-2+ cells also produced IFN-gamma in vitro, provided accessory cells (plastic-adherent and Thy-1- Ia- splenocytes, respectively) were added to the lymphocyte-yeast cell cocultures. The production of IFN-gamma by purified L3T4+ and Lyt-2+ cells was inhibited by addition of the respective anti-class II and anti-class I H-2 antibody to the cultures. In vivo, administration of anti-L3T4, anti-Lyt-2.2 mAb or a combination of both significantly impaired the resistance of immunized mice to challenge with virulent C. albicans, as manifested by increased recovery of the yeast from the mouse kidneys. A similar effect was observed upon neutralization of endogenous IFN-gamma by treatment with rat mAb. These results suggest that both L3T4+ and Lyt-2+ T cells play a role in acquired immunity to systemic C. albicans infection, and that their activity may involve IFN-gamma-mediated stimulation of candidacidal mechanisms.

Animals↗
PubMed1989

Delayed-type hypersensitivity to tumor antigens co-expressed with immunogenic determinants induced by xenogenization.

Previous work has shown that murine lymphoma cells antigenically altered ("xenogenized") by drug treatment elicit strong in vivo resistance to the original cells. Moreover, splenocytes immune to a drug-treated variant (L5178Y/DTIC) of a murine lymphoma exert anti-parental tumor activity in an adoptive transfer system, an effect mediated by L3T4+ lymphocytes and associated with the detection of an anti-L5178Y delayed-type hypersensitivity (DTH) response. We now report that the in vivo activity of the tumor-immune L3T4+ lymphocytes is a radio-sensitive (2,500 rad in vitro) phenomenon that requires collaboration with radio-resistant, silica-sensitive syngeneic cells in the host, and is inhibited by treatment of recipient mice with monoclonal antibodies (MAbs) to the L3T4 antigen or murine interferon-gamma (IFN-gamma). In vitro, the tumor-immune L3T4+ lymphocytes produce interleukin 2 (IL-2), lymphotoxin (LT) and IFN-gamma activities on incubation with L5178Y cells and spleen-adherent cells. These results suggest that the mechanisms of anti-parental tumor protection by xenogenized cells involve specific induction of a DTH response mediated by the "inflammatory" (THI) subset of L3T4+ T lymphocytes and IFN-gamma activated macrophages.

Animals↗
PubMed1989

Protective immunity induced by low-virulence Candida albicans: cytokine production in the development of the anti-infectious state.

A low-virulence, agerminative strain of Candida albicans (PCA-2) is able to confer a high degree of nonspecific protection against subsequent challenge with highly virulent microorganisms in mice. In an attempt to better define the effect of PCA-2 vaccination on the immune system and the nature of the mechanisms involved in this protective state, we evaluated the pattern and kinetics of production of selected cytokines in PCA-2-treated mice. Thus, granulocyte/monocyte colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin 1 (IL-1) were measured in the sera and spleen cell supernatants of vaccinated mice. In both cases, high levels of CSF, TNF, IL-1, and IFN were found 6 hr after PCA-2 infection and persisted for many days. There was always a correlation between the ability of PCA-2 to induce antimicrobial protection in vivo and its ability to cause cytokine production in vitro. Supernatants of splenocyte cultures from PCA-2-infected animals possessed macrophage-activating activity, as measured in microbiological assays. These data suggest an important involvement of cytokines in the nonspecific anti-infectious immunity induced by PCA-2, and also suggest a crucial role for IL-1 as an endogenous adjuvant in the initiation of the immune response to PCA-2.

Amphotericin B↗
PubMed1989

Cell-mediated immunity to chemically xenogenized tumors--IV. Production of lymphokine activity by, and in response to, highly immunogenic cells.

To determine whether a novel pattern of lymphokine production might be involved in the superior immunogenicity of chemically xenogenized tumors over that of parental cells, we tested a panel of murine tumors xenogenized by DTIC for production of soluble factors with lymphokine-like activity and induction of lymphokine release from naïve or specifically sensitized lymphocytes. In the L5178Y tumor system, a majority of xenogenized but not parental clones produced an IL-1-like factor, and this was associated, as a rule, with class II antigen expression and antigen-presenting ability. However, no such properties were exhibited by the xenogenized variants of P815 and L1210Ha cells, which nevertheless occasionally expressed other lymphokine (GM-CSF, IL-3) activities. On examining the ability of xenogenized and parental tumors to cause release of IL-1, IL-2, IL-3, IFN-gamma, TNF/LT and GM-CSF from T-cells, we found, as a rule, an increased lymphokine production when lymphocytes primed in vivo to a xenogenized tumor were restimulated in vitro with the same or parental cells.

Animals↗
PubMed1989

Immunosuppressive effect of cyclosporin A on resistance to systemic infection with Candida albicans.

We studied the influence of cyclosporin-A (Cy-A) on resistance of mice to systemic infection with Candida albicans. Cy-A clearly inhibited resistance to C. albicans. The effect was dose-dependent and time and route of administration of the drug were important. This immunodepressive effect was due, at least in part, to an impairment of polymorphonuclear leucocyte (PMNL) candidacidal activity, as demonstrated in vitro by a reduction of phagocytic and cytotoxic activity and in vivo by protection when PMNL from untreated mice were transferred into cyclophosphamide-treated hosts challenged with C. albicans. The decreased activity of PMNL could be partly restored by adoptive transfer of normal T-lymphocytes into Cy-A-treated mice, as well as by exposure of PMNL to gamma-interferon (IFN-gamma) in vitro.

Animals↗
PubMed1989

Role of L3T4+ lymphocytes in protective immunity to systemic Candida albicans infection in mice.

Protective immunity to lethal Candida albicans challenge in vivo and activation of splenic macrophages with highly candidacidal activity in vitro were detected in mice infected with low-virulence agerminative yeast cells of the variant strain PCA-2, at a time when a strong delayed-type hypersensitivity (DTH) reaction to C. albicans occurred in the footpads of PCA-2-treated mice. The DTH reaction was transferable with spleen cell populations from these animals, and enrichment of splenic lymphocytes in L3T4+ cells significantly increased the footpad swelling. The reactivity transferred by L3T4+ cells was a radiosensitive (2,500 rads in vitro) phenomenon that required collaboration with radioresistant, silica-sensitive syngeneic cells in the host and was inhibited by treatment of recipient mice with antibodies to the L3T4 antigen or murine gamma interferon. In vitro, the PCA-2-immune L3T4+ cells produced various lymphokine activities upon incubation with C. albicans, including gamma interferon and granulocyte-macrophage colony-stimulating factor. Anti-L3T4 monoclonal antibody treatment of PCA-2-infected mice significantly impaired their footpad reaction and resistance to C. albicans, as shown by increased recovery of yeast cells from the kidneys of anti-L3T4-treated mice. These results suggested that the mechanisms of anti-Candida resistance induced by PCA-2 may involve specific induction of a DTH response mediated by inflammatory L3T4+ T cells and lymphokine-activated phagocytic effectors. However, the survival rate of the PCA-2-immune mice challenged with C. albicans was not significantly modified by administration of the anti-L3T4 antibody, thus allowing for the conclusion that compensatory mechanisms lead to considerable anti-Candida resistance when the activity of L3T4+ cells is deficient.

Animals↗