Search PubMed⌕ Search

Biomedical subjects

F Dieli

Publications and source records attributed to F Dieli.

At least 55 records · Page 3Linked to original sources
PubMed1997

TCR V alpha chain expression influences reactivity to the hapten TNP.

We have recently demonstrated a remarkable selection of in vitro cultivated, TNP-specific polyclonal T cell lines for the expression of a TCR beta chain encoded by the V beta 8.2 gene. The goal of the present study was to analyse V alpha usage in V beta 8.2 T cells responsive to TNP, using TNP-specific T cell lines derived from three common strains of mice, as well as from V beta 8.2 transgenic mice. Results indicate that in vitro TNP stimulation of T cells from TNP-immune mice results in significant skewing of V alpha usage among responding V beta 8.2+ T cells, with overexpression observed for V alpha 3.2 and V alpha 8. These results indicate that V alpha expression influences recognition of TNP by T cells, and suggest that the hapten TNP might be recognized like typical peptide antigens by combinatorial TCR alpha and beta contact sites.

Animals↗
PubMed1996

Interleukin 4 suppresses primary interferon gamma response by T cells immunized in vivo and cultured in vitro with interleukin 2.

This paper describes a novel primary in vivo/in vitro culture system which allows analysis of the effect of IL-4 added to culture 1 day after immunization on the production of IFN-gamma. Mice are immunized epicutaneously with picryl chloride (TNP) and draining lymph node cells were harvested 1 day later. These cells (1 day lymph node cells), when cultured in vitro for 3 days in the presence of IL-2, either continuously or as a pulse, give an IFN-gamma response on reexposure to antigen 3 days later. This production of IFN-gamma is both antigen-specific and genetically (MHC)-restricted and is due to both CD8+ and CD4+ T cells. However, if 1 day lymph node cells are cultured with both IL-2 and IL-4, no IFN-gamma is produced on subsequent reexposure to antigen, but the cells acquire the ability to produce IL-4 and IL-10. Moreover, cells pulsed with IL-4 blocked IFN-gamma production when cocultured with cells pulsed with IL-2. IL-4 only exerted its inhibitory activity on IFN-gamma production when added on the first or second day of culture and had no effect at later times. Finally, the inhibitory activity of IL-4 on IFN-gamma production may depend on the production of IL-10, induced by the IL-4, as the inhibitory effect of IL-4 is reversed by mAb against IL-10.

Animals↗
PubMed1996

Cytokine production pathway in the elderly.

It is well known that aging is associated with various alterations in lymphoid cell functions, particularly with a progressive decline in immune responsiveness to exogenous antigens and increasing incidence of autoimmune phenomena. Many studies have been focused on the mechanisms of the immunologic features of aging. this review describes our results of studies performed to determine the influence of age on the capacity to produce interleukin-2 (IL-2), interferon-gamma (IFN-gamma), interleukin-4 (IL-4), interleukin-t (IL-5), interleukin-6 (IL-6) and tumor necrosis factor (TNF). Mitogen-stimulated cultures of mononuclear cells (MNC) from human beings were assessed for cytokine-producing capacity. A significant decrease in IFN-gamma and IL-2 production by MNC cultures from elderly individuals was observed. No significant difference was instead observed between cultures from elderly individuals and those from young ones as regards TNF-alpha, IL-4 and IL-6 production. Mitogen or antigen-stimulated cultures of MNC from aged mice also displayed a significant decrease in IFN-gamma and IL-2 production as well as TNF-beta. Instead IL-4 and IL-5 production significantly increased in these cultures. We suggest that this imbalanced cytokine production may well account for the pattern of immune response which may be observed in the elderly, i.e. a normal or increased humoral response (including autoimmune responses) in face of a low T cell immune responsiveness.

Aged↗
PubMed1996

Role of IL-4 in delayed type hypersensitivity.

IL-4 plays a key role in the contact sensitivity skin reaction. This has several implications. First, the view that contact sensitivity (CS) is only mediated by cells with a Th1 profile of cytokine secretion needs modification, in the light of the essential role of IL-4 at the effector stage. Second, the concept of a single cell involved in the systemic transfer of CS is no longer tenable, as it is known that both alpha beta and gamma delta cells are required. Studies with the cell lines (which contain both alpha beta and a few gamma delta cells) suggest that this double requirement may involve the action of IL-4 on gamma delta cells, which bear receptors for IL-4. Finally, the view that T cell lines only transfer CS when injected locally, but not when injected intravenously (systemic transfer), is correct but incomplete, as T cell lines actually give systemic transfer of CS, providing the cell line or the recipient is treated with IL-4.

Animals↗
PubMed1996

Major histocompatibility complex regulation of cytokine production.

This review describes the phenomenon of the major histocompatibility complex (MHC) control of cytokine production both in experimental animals and in humans. H-2 (mouse MHC) regulates which type of cytokine is selectively produced in response to the hapten trinitrophenyl (TNP). T cells from TNP-immune H-2k mice produce interferon-gamma (IFN-gamma), interleukin-2 (IL-2), IL-3, IL-5, tumor necrosis factor-alpha (TNF-alpha), IL-10, and very low levels of IL-4 on reexposure to the specific antigen in vitro. By contrast, T cells from H-2d mice produce IL-3, TNF-alpha, IL-10, and IL-4 but very low levels of IL-2, IL-5 and IFN-gamma. As MHC-congenic matched strains (BALB/k and BALB/c) are used, this makes it unlikely that non-MHC genes influence the class of response observed. A similar pattern of haplotype regulation of cytokine production is observed in humans. In fact, peripheral blood mononuclear cells from HLA-B8,DR3-positive and negative individuals differ in their ability to produce IL-2, IL-5, and IFN-gamma on stimulation with the mitogen phytohemagglutinin while producing similar amounts of IL-4, IL-6, and IL-10. The following main considerations emerge from these observations. The MHC/peptide complex generated after antigen immunization, indicates which class of cytokine production is preferentially induced and, therefore, the outcome of the immune response. Furthermore, MHC genotype may affect cytokine production (and then immune responses) by completely different mechanism(s), that is, by an antigen-nonspecific control that does not depend on the ability of MHC molecules to bind in different ways the different peptides. Accurate control of the functional repertoire of an immune response is a critical parameter in response to infections as well as in immunopathology. MHC control of the class of the immune response at the level of cytokine production is a sophisticated way in which this occurs. This control might be involved in adaptive immune responses to infections as well as in immunopathology.

Animals↗
PubMed1996

Control mechanisms of cell-mediated reactions.

One of the most relevant aspects of tumor adoptive immunotherapy is provided by clinical trails on transfer of cytotoxic cells (LAK and TIL). However, LAK cell therapy is effective in a small number (16-22%) of only certain tumors, while therapy with TIL cells is efficient in about 40% of melanomas. Several possibilities have been raised to explain the low efficacy of cytotoxic cells in tumor therapy, amongst which are the poor immunogenicity of tumor and tumor-induced immunodepression. Furthermore, the possibility that cytotoxic cells do not reach the tumor site in adequate numbers has to be considered. We have developed an experimental system to study the ability of antigen-specific T cells to reach the target antigen in the tissues. The results obtained demonstrate that gamma delta cells and IL-4 are required to allow tissue localization of antigen-specific alpha beta cells, thus indicating that their ability to exert certain effect or functions requires cooperation by other cells types. These results may be relevant to the understanding of the mechanisms leading to localization of immunologically active cells at a tumor site.

Animals↗
PubMed1996

Evidence of induced non-tolerance in HLA-identical twins with hemoglobinopathy after in utero fetal transplantation.

Fetus-to-fetus transplantation has been suggested for the treatment of hemoglobinopathies in utero. However, dissimilar results have to date been obtained by different groups. We describe a case in which fetus-to-fetus transplantation in HLA-identical twins was performed at the 19th week of gestation by infusion of 0.8 ml of fetal blood from normal to beta-thalassemia affected fetus with the main aim of inducing tolerance. No evidence of engraftment, determined by KM19 polymorphism, was present after 2 years of the procedure. Moreover, an alloreactive cytotoxic T lymphocyte precursor (CTLp) study of affected fetus vs donor and other different stimulators showed that immunization vs tolerance was the real effect of the procedure.

Adolescent↗
PubMed1995

IL-5 enhances in vitro and in vivo antigen-specific IgA production in MHC genetically determined low IL-5 responder mice.

Lymphonode cells from BALB/k mice, but not from BALB/c mice, immunized with picryl chloride (PCl) produce IL-5 when stimulated with the specific antigen in vitro and this correlates with picryl-specific IgA levels in vivo, which are 6 to 10 times higher in BALB/k mice. B lymphocytes from BALB/k mice cultured with PCl-immune T cells from BALB/k produce in vivo anti-PCl-IgA, while B lymphocytes from BALB/c mice, cultured with T cells from BALB/c mice, fail to produce appreciable amounts of anti-PCl IgA, unless IL-5 is added to cultures. B lymphocytes from both strains of mice produce similar amounts of total IgA antibodies when stimulated in vitro with lipopolysaccharide. In vivo administration of IL-5 to BALB/c mice increases significantly PCl-specific IgA levels to those observed in BALB/k mice and a dose-response analysis reveals that 500 units of IL-5 was the minimal effective dose, although a small increase in PCl-specific IgA levels was observed with 100 units of IL-5. Total IgA levels were increased in both strains of mice following in vivo injection of IL-5, but no significant difference in the values was observed. Our results therefore indicate that IL-5 in vivo enhances antigen-specific IgA production in MHC-determined low IL-5 responder mice and suggest an explanation for IgA deficiency in humans.

Animals↗
PubMed1995

Major histocompatibility complex control of the class of the immune response to the hapten trinitrophenyl.

This paper investigates major histocompatibility complex (MHC) regulation of the class of the immune response given in vitro and in vivo following immunization of the congenic BALB/k (H-2k) and BALB/c (H-2d) mice with the hapten trinitrophenyl (TNP). TNP-immune lymph node cells from BALB/k mice produced high levels of interferon-gamma (IFN-gamma), interleukin-5 (IL-5) and IL-2 when stimulated with TNP-antigen-presenting cells (APC) in vitro, while TNP-immune lymph node cells from BALB/c mice produced very low levels of these cytokines. No significant difference was found in antigen-specific production of IL-3, IL-4 and tumour necrosis factor-alpha (TNF-alpha). There was a strong correlation between the pattern of cytokine production in vitro and the secondary antibody production in vivo. Sera from BALB/k mice had anti-TNP IgG2a, IgG2b and IgG3 levels threefold greater, and anti-TNP IgA levels eightfold greater, than BALB/c mice. The level of specific IgG1 and IgE was only marginally raised in BALB/k mice. In contrast to these strain differences in cytokine and antibody production, there was no difference in two measures of cellular immunity: contact sensitivity in vivo and antigen-specific lymphocyte response in vitro. Our results suggest that there is a good correlation between the production of cytokines in vitro and antibody response in vivo, but not with measures of cellular immunity. Moreover, this MHC control of the class of the immune response to TNP does not fit into the T-helper type-1 (Th1)-Th2 paradigm.

Animals↗
PubMed1995

Interleukin-4 is a critical cytokine in contact sensitivity.

This study demonstrates an essential role for interleukin-4 (IL-4) in the delayed hypersensitivity reaction, as illustrated by contact sensitivity (CS) to trinitrochlorobenzene (TNCB). Injection of mice with monoclonal antibody to IL-4, but not with control antibody, reduced CS after active immunization by 75%, as judged by ear swelling. The histological alterations of CS were also reduced. IL-4 was essential to the effector stage, as inhibition of its production or action blocked the passive transfer of CS. In particular, treatment of immune lymph node cells with antisense oligonucleotide to IL-4 inhibited the systemic transfer of CS. Transfer was also inhibited by monoclonal antibody to IL-4 given to the recipient. The present results indicate that IL-4 is an essential cytokine at the effector stage of the CS reaction.

Animals↗
PubMed1994

IL-4 is essential for the systemic transfer of delayed hypersensitivity by T cell lines. Role of gamma/delta cells.

Hapten (trinitrophenyl)-specific T cell lines were obtained by repeated stimulation of lymph node cells from immune mice with Ag in vitro. These T cell lines show phenotypic properties and a pattern of cytokine production typical of Th1 cells and consisted of more than 90% V beta 8.2+ T lymphocytes and 6 to 9% gamma/delta + T lymphocytes. The lines mediate a local passive transfer of DTH when injected at the site of Ag challenge but fail to mediate a systemic passive transfer of DTH when injected i.v. However, a successful systemic passive transfer of DTH was observed when IL-4 was given to recipient mice together with the T cell lines or when the T cell lines were incubated in vitro with IL-4. IL-4 enables systemic, specific passive transfer of DTH at a dose of 10 pg/ml in vitro and at a dose of 10 pg/mouse in vivo; it is effective when injected 4 h before cell transfer but not when given 1 to 5 days earlier. Cytofluorimetric analysis shows that the gamma/delta + cells and not the V beta 8.2+ cells of the line express IL-4R and a good systemic transfer of DTH is observed when gamma/delta + cells are incubated in vitro with IL-4 and then injected together with V beta 8.2+ cells into recipient mice. In contrast, injection of V beta 8.2+ cells treated with IL-4 together with gamma/delta + cells fails to transfer DTH. Overall, the present results show that IL-4 is an important mediator in the DTH reaction and that gamma/delta + cells are one of the targets of its action.

Animals↗
PubMed1994

I-J revisited: is the I-J genetic restriction in downregulation due to an endogenous superantigen analogous to mammary tumour virus (Mtv)-encoded endogenous superantigen?

This article puts forward the hypothesis that the I-J genetic restriction observed between certain downregulatory (suppressor) T cells and antigen presenting cells is due to an endogenous superantigen analogous to the mouse mammary tumour virus (Mtv) products encoded by the open reading frames in the 3' long terminal repeat (LTR) of mtv's. In its weak form this hypothesis asserts that the I-J genetic restriction is due to an endogenous superantigen ligand on antigen presenting cells, which crosslinks the V beta and/or V alpha chains of certain T cell receptors (TCR) with major histocompatibility complex (MHC) class II, and that MHC together with this superantigen ligand causes positive selection of T cells bearing the appropriate I-J+ TCR in the thymus. In the periphery these T cells recognize peptide/MHC complex in the presence of the superantigen. In its strong form the hypothesis states that this superantigen ligand for TCR and MHC is encoded by integrated virus genome, e.g. Mtv. These possibilities can now be approached experimentally and their exploration may uncover one of the ways in which T cells are assigned to different functions, including downregulation.

Animals↗
PubMed1994

Dominant V beta 8 gene usage in response to TNP: failure to use other V beta chains following removal of V beta 8+ T cells by monoclonal antibody in vivo.

This paper investigates the V beta usage of lymph node cells from mice immunized with TNP and of cell lines made from them. In cell lines stimulated weekly with TNP in vitro for 1 month, about 87% of the cells were V beta 8+ and further analysis showed that these cells were actually V beta 8.2+. This was also true for the cells that proliferated in lymph nodes in response to TNP 4 days after primary immunization, i.e. proliferation occurred mainly in the V beta 8+, and in particular in the V beta 8.2+, population while much less proliferation occurred when the V beta 8- or V beta 8.2- T-cell populations are used. This was not due to non-specific damage during separation, as the response to concanavalin A and alloantigen was intact. In a separate series of experiments, mice were acutely depleted of V beta 8+ T cells by treatment with F23.1 or a control monoclonal antibody (mAb) in vivo given before immunization. Treatment with the relevant mAb virtually abolished the response to TNP. In contrast, SJL mice, which lack the gene segment coding for the V beta 8 family and several other V beta chains, made a normal proliferative and delayed-type hypersensitivity (DTH) response to TNP. This poses the problem, which may be important in the study of the T-cell repertoire, of why acute removal of V beta 8+ T cells, which are dominantly used in the response to TNP, does not allow T cells using other chains to substitute in the response, while the absence of this population over a long period of time, because of a deletion in the genome, allows the use of T cells bearing other V beta chains.

Animals↗
PubMed1993

Major histocompatibility complex regulation of interleukin-5 production in the mouse.

Lymph node cells of CBA (H-2k), but not of BALB/c (H-2d) mice immunized epicutaneously with picryl chloride secrete interleukin (IL)-5 when stimulated with the specific antigen in vitro. The low IL-5 production in BALB/c mice persists when either picryl chloride or the unrelated antigen oxazolone are used, when the amount of antigen in vitro is varied and when a secondary response is studied. The difference in IL-5 production maps to the major histocompatibility complex (MHC) in the congenic BALB/b, BALB/c and BALB/k mice. Furthermore, lymph node cells from (k x d) F1 mice produce IL-5 when stimulated by antigen presented on H-2k but not on H-2d antigen-presenting cells. Finally, the low IL-5 production in vitro in BALB/c mice is correlated with low picryl-specific IgA levels in vivo, which otherwise are ten times greater in CBA and BALB/k mice. The influence of MHC on IL-5 production and IgA secretion in the mouse might be a possible basis for the association of MHC with IgA deficiency in humans.

Animals↗
PubMed1993

Augmented passive transfer of contact sensitivity in severe combined immunodeficiency mice and its dependence of V beta 8+ cells in the picryl system.

The passive transfer of contact sensitivity using picryl chloride immune cells from H-2 syngenic BALB/c donors was analyzed in severe combined immunodeficiency (SCID) mice which lack functional T and B lymphocytes. H-2-restricted and antigen-specific contact sensitivity was transferred to SCID mice, and comparison between the level of contact sensitivity and the number of transferred cells showed a significantly more efficient transfer to SCID than to BALB/c mice. The cells passively transferring contact sensitivity were shown to carry the V beta 8 phenotype. Moreover, chromium-labeled cells from BALB/c PC1-primed donors localize normally in peripheral lymphoid organs and an increased percentage of cell arrival in the ears is clearly observed in SCID after challenge with picryl chloride.

Animals↗
PubMed1992

A nonspecific inhibitor of contact sensitivity elaborated by macrophages: genetic restriction in its production but not in its action.

It is known that macrophages armed with hapten-specific T suppressor factor (TsF) and then exposed to antigen (haptenized spleen cells) liberate a nonspecific inhibitor of the transfer of contact sensitivity (CS). This is called macrophage suppressor factor (MSF). This paper shows that MSF is only released when the source of the TsF and the haptenized spleen cells share the same I-J subregion. This is based on the comparison of B10.A(3R) and B10.A(5R) mice. In contrast, the action of MSF is antigen nonspecific and genetically unrestricted. In these respects it resembles the antigen-nonspecific inhibitor (nsTsF-1) made by the T acceptor cell when armed with TsF. However, it differs from nsTsF-1 in acting directly on the I-A- population which transfers contact sensitivity and not indirectly via I-A+ T cells. In vitro, MSF fails to inhibit the proliferative response of lymph node cells to specific antigen and their production of IL-3 activity, IFN-tau, and IL-2. This indicates that MSF is not a global inhibitor of T cell activity. The finding that MSF inhibits systemic passive transfer of contact sensitivity, but has no effect on local passive transfer strongly supports the view that MSF affects the arrival of certain cells critical for the development of the reaction to the skin challenge site.

Animals↗