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L V Rizzo

Publications and source records attributed to L V Rizzo.

48 records · Page 3Linked to original sources
PubMed1995

The use of oral tolerance as a therapy for ocular autoimmunity.

Mucosal surfaces throughout the body are the main protective structures against the heavy antigen burden from the environment. The ability to distinguish between noxious agents that should be kept in check and innocuous or beneficial substances that should be ignored is one of the most interesting phenomenon in immunology. Oral tolerance is the phenomenon by which exposure to a soluble antigen through the mucosal surface results in subsequent inability to mount an immune response to the same antigen upon challenge by a different route. This type of tolerance-inducing mechanisms has been recognized for many years as an effective approach to induce peripheral tolerance to soluble proteins. Recent achievements in the use of oral tolerance in the treatment of autoimmune diseases are reviewed here. Special emphasis is placed on the use of this immunotherapeutic approach to uveitis. The role of cytokines, CD4+ cells, CD8+ cells, as well as the putative mechanisms by which oral tolerance is induced, are discussed.

Autoimmune Diseases↗
PubMed1994

Interleukin-2 treatment potentiates induction of oral tolerance in a murine model of autoimmunity.

The present study addresses the feasibility of potentiating oral tolerance by immunomanipulation, using the murine model of experimental autoimmune uveoretinitis (EAU) induced by immunization with the retinal antigen interphotoreceptor retinoid binding protein (IRBP). Three feedings of 0.2 mg IRBP every other day before immunization did not protect against EAU, whereas a similar regimen of five doses was protective. However, supplementing the nonprotective 3x regimen with as little as one injection of 1,000 U of human recombinant interleukin-2 (IL-2) resulted in disease suppression that was equal to that of the protective 5x regimen. The protective effect was maintained across a range of IL-2 doses and times of administration; none of the IL-2 regimens tested resulted in disease enhancement. Peyer's Patch cells of 3x-fed and IL-2-treated mice showed greatly increased production of TGF-beta, IL-4, and IL-10 compared with animals given the nonprotective 3x regimen and to animals given the protective 5x regimen. We propose that IL-2 treatment enhances protection from EAU at least in part by stimulating production of antiinflammatory cytokines by regulatory cells in Payer's Patches. Moreover, the observed lymphokine production patterns suggest that whereas protection induced by the 3x + IL-2 regimen is likely to involve antiinflammatory cytokines, protection induced by the 5x regimen might involve anergy or deletion of the uveitogenic T cells. These results could have practical implications for use of IL-2 as a safe and effective way of potentiating oral tolerance.

Administration, Oral↗
PubMed1993

Induction of immunoglobulin synthesis by CD4+ T cell clones.

The study of mechanisms by which CD4+ T cells induce Ig synthesis has been greatly enhanced by the availability of CD4+ T cell clones with restricted cytokine profiles. We have demonstrated with in vitro and in vivo studies that both Th1 (T helper cell 1) and Th2 clones can provide MHC restricted help and induce primary as well as secondary antibody responses under cognate antigen driven conditions. In addition, we have shown that both types of clones, utilizing distinct cytokines, can effect B cell memory and affinity maturation of the Ig response, although the precise mechanisms by which this occurs are not yet clear. Using Th1 and Th2 clones, we have also shown that the pathways for IgG1 synthesis are redundant, in that induction of IgG1 synthesis in secondary responses in which B cells have already switched from IgM to IgG1, can occur via several pathways, one involving IL-4 and IL-5, the other involving IL-2. In contrast, IgE and IgG2a synthesis require specific cytokines for synthesis in both primary and secondary B cells. Finally, the cytokines produced by Th1 and Th2 clones can 'neutralize' each other, when both types of clones are present during the induction of primary Ig responses. As an exception however, the induction of IgA synthesis is greatly augmented by the presence of both types of clones.

Animals↗
PubMed1992

Generation of B cell memory and affinity maturation. Induction with Th1 and Th2 T cell clones.

We used an adoptive transfer system and CD4+ T cell clones with defined lymphokine profiles to examine the role of CD4+ T cells and the types of lymphokines involved in the development of B cell memory and affinity maturation. Keyhole limpet hemocyanin (KLH)-specific CD4+ Th2 clones (which produce IL-4 and IL-5 but not IL-2 or IFN-gamma) were capable of inducing B cell memory and affinity maturation, after transfer into nude mice or after transfer with unprimed B cells into irradiated recipients and immunization with TNP-KLH. In addition, KLH-specific Th1 clones, which produce IL-2 and IFN-gamma but not IL-4 or IL-5, were also effective in inducing B cell memory and high affinity anti-TNP-specific antibody. The induction of affinity maturation by Th1 clones occurred in the absence of IL-4, as anti-IL-4 mAb had no effect on the affinity of the response whereas anti-IFN-gamma mAb completely blocked the response. Th1 clones induced predominantly IgG2a and IgG3 antibody, although Th2 clones induced predominantly IgG1 and IgE antibody. We thus demonstrated that some Th1 as well as some Th2 clones can function in vivo to induce Ig synthesis. These results also suggest that a single type of T cell with a restricted lymphokine profile can induce both the terminal differentiation of B cells into antibody secreting cells as well as induce B cell memory and affinity maturation. Moreover, these results suggest that B cell memory and affinity maturation can occur either in the presence of Th2 clones secreting IL-4 but not IFN-gamma, or alternatively in the presence of Th1 clones secreting IFN-gamma but not IL-4.

Animals↗
PubMed1992

Differential modulatory effect of IL-5 on MHC class II expression by macrophages and B cells.

The present study examines the effect of interleukin 5 on the expression of class II major histocompatibility complex (MHC) in macrophages and B cells. Treatment of splenic adherent cells, a population that contains mostly macrophages and dendritic cells, with 100 U/ml of recombinant interleukin 5 resulted in a decrease of 10 to 30% in cell surface MHC class II expression by macrophages. The treatment had no effect on class I MHC expression, or on the mRNA synthesis as evaluated by tritiated-uridine incorporation. The same treatment of B cells resulted in the delineation of two groups with regard to class II MHC expression in a previously more homogeneous population. One group had an increase in surface Ia expression and the other had a decrease in the expression of this molecule. These results suggest that interleukin 5 has a role in MHC class II regulation.

Animals↗
PubMed1991

Differential regulation of antigen presentation in high- and low-IgE responder mice.

Strains of mice differ greatly in their capacity to produce interleukin (IL) 4 and high levels of serum IgE. The contribution of macrophages (M phi) in enhancing the production of IL4 by T cells in high-IgE responder mice was studied. M phi from BALB/c mice (high-IgE responder strain) developed an augmented capacity to present antigen to IL 4-producing T helper type 2 (Th2) clones, when the M phi were pretreated by exposure to the lymphokines IL 4 and IL 5. In contrast, identical treatment of M phi from H-2-identical DBA/2 mice (low-IgE responder strain) resulted in inhibition of the capacity to stimulate Th2 clones. The impairment of antigen presentation by DBA/2 M phi was closely paralleled by a decrease of cell surface class II major histocompatibility complex (MHC) expression and an abrogation of IL 1 production by these cells, while identical treatment of BALB/c M phi enhanced class II MHC expression and did not inhibit secretion of IL 1. Our studies demonstrate that IL 4 and IL 5 can exert different effects on M phi from high- and low-IgE responder strains of mice, resulting in down-regulation of the expansion of IL 4-producing cells in low-but not high-IgE responder mice.

Animals↗
PubMed1990

Malignant, non-Hodgkin's lymphomas in Trypanosoma cruzi-infected rabbits treated with nitroarenes.

Use of 2-nitroimidazole, 5-nitrofuran and 5-nitroimidazole compounds in T. cruzi-infected rabbits resulted in a reduction in duration of parasitaemia in comparison with untreated, infected rabbits. The chronic myocarditis associated with Chagas' disease was not, however, prevented in nitroarene-treated rabbits; lymphocytic infiltrates associated with cardiac cell lysis, in the absence of parasites in situ, were present in both treated and untreated rabbits. The carcinogenic effect of each trypanocidal nitroarene used in this study was also assessed. Administration of nitroarenes to rabbits resulted in the appearance of solid tumours in 37.8 per cent of animals that received drug therapy. Untreated, control rabbits in this series did not show tumour growth. Furthermore, malignant, mixed-cell type, non-Hodgkin's lymphomas were seen in 32.4 per cent of the treated rabbits. It seems that a direct relationship could be present between the presence of the nitro group, the trypanocidal cytotoxicity and the prevalence of tumours. Benznidazole cleared up parasitaemias in the shortest time and was associated with 41.6 per cent of lymphoma growths, whereas MK-436 required twice as much time to clear blood parasites, and showed lymphomas in 25 per cent of experimental rabbits. The demonstration of a high prevalence of malignant tumours in addition to the chronic myocarditis of Chagas' disease in nitroarene-treated rabbits is important since indiscriminate use of such compounds currently used to treat T. cruzi infections in man could increase the risk of lymphoma.

Animals↗
PubMed1989

Autoimmunity in Chagas' disease: specific inhibition of reactivity of CD4+ T cells against myosin in mice chronically infected with Trypanosoma cruzi.

In this study, we assessed the proliferative response of T cells from mice chronically infected with Trypanosoma cruzi to actin, myosin, or T. cruzi soluble antigen (SA). We report here that CD4+ T cells from mice chronically infected with T. cruzi proliferated in response to myosin but not to actin, whereas cells from naive mice did not proliferate against any of the antigens tested. Antisera raised against myosin- or SA-activated T cells specifically inhibited respectively, the myosin or SA in vitro proliferative response, whereas the response to unrelated antigen remained unimpaired. Sera from chronically infected mice failed to show any significant inhibitory activity. The above findings suggest that autoreactive and T. cruzi-reactive T cells belong to different, perhaps nonoverlapping, compartments of the immune cell repertoire of mice chronically infected with T. cruzi. The failure of infected mice to trigger the suppressive mechanisms described here might be the primary immune defect leading to breakdown of self-tolerance and unopposed, perhaps tissue-damaging, autoimmunity in experimental Chagas' disease.

Adjuvants, Immunologic↗
PubMed1989

Prostaglandin E2 inhibits proliferation but not interleukin-2 production by phorbol ester plus calcium ionophore-activated murine T cell clones.

1. We have investigated the effect of prostaglandin E2 (PGE2) on the T lymphocyte activation pathway. 2. At physiologically attainable concentrations (approximately 0.1 microM), PGE2 effectively inhibited the proliferation of murine antigen-specific "helper" T cell clones stimulated either with specific antigen in the presence of macrophages or with phorbol ester plus calcium ionophore A23187. The inhibition was not reversed by the addition of exogenous Interleukin 2 (IL-2) in either case. 3. PGE2 treatment at the same concentrations did not inhibit IL-2 production by phorbol ester plus calcium ionophore-stimulated T cell clones as assayed by CTLL proliferation. 4. These results suggest that the major target (or targets) of PGE2 inhibition directly on T cells lies in the IL-2 signal transduction pathway rather than in the early activation events leading to T cell activation.

Animals↗