A number of features occurring during host-parasite interactions in Chagas disease caused by the protozoan parasite, Trypanosoma cruzi, and Leishmaniasis, caused by a group of kinetoplastid protozoan parasites are reminiscent of those observed in cancer diseases. In fact,although the cancer is not a single disease, and that T.cruzi and Leishmania are sophisticated eukaryotic parasites presenting a high level of genotypic variability the growth of the parasites in their host and that of cancer cells share at least one common feature, that is their mutual capacity for rapid cell division. Surprisingly, the parasitic diseases and cancers share some immune evasion strategies. Consideration of these immunological alterations must be added to the evaluation of the pathogenic processes. The molecular and functional characterization of virulence factors and the study of their effect on the arms of the immune system have greatly improved understanding of the regulation of immune effectors functions. The purpose of this review is to analyze some of the current data related to the regulatory components or processes originating from the parasite that control or interfere with host cell physiology. Attempts are also made to delineate some similarities between the immune evasion strategies that parasites and tumors employ. The elucidation of the mode of action of parasite virulence factors toward the host cell allow not only provide us with a more comprehensive view of the host-parasite relationships but may also represent a step forward in efforts aimed to identify new target molecules for therapeutic intervention.
The effect of oral administration of lactoferrin (LF) was studied to determine if it could modify post-surgical immune response. The action of lactoferrin was evaluated in 18 LF-treated patients versus 28 placebo counterparts. Patients (women and men, mean age 50 years) were given daily oral doses (20 mg each) of LF for 5 consecutive days prior to thyroid surgery. The following immune response parameters were determined in blood samples taken from the patients one day before, one day after, and 5-7 days following surgery: cell morphology, the proliferative response of peripheral blood mononuclear cells (PBMC) to phytohemagglutinin (PHA), and the spontaneous and lipopolysaccharide (LPS)-induced production of tumor necrosis factor alpha (TNF-) and interleukin 6 (IL-6). As a consequence of the thyroid surgery, the total leukocyte count increased on the postoperative day by about 50% in all patients and the percentage of lymphocytes fell by 26 and 35% in the control vs LF-treated group. The content of neutrophils, on the other hand, elevated on day 1 post-operation by 51 and 68%, respectively. The percent of neutrophil precursors was markedly higher in LF-treated patients, particularly on the day before and the day after surgery (4.1 and 4.8 vs 2.5 and 3.7%, respectively). The post-surgical values were, however, comparable in both groups for neutrophils. The proliferative response of lymphocytes showed a slight decrease in the control group and an increase in the LF-treated patients on day 5 post-operation (20% over control group). LPS-induced TNF- production was higher in LF-treated patients in both one day before and one day following surgery (28 and 24% respectively). LPS-induced IL-6 production was comparable in both placebo and LF-treated patients before surgery, however, on day 1 and 5 following surgery, the production of IL-6 was higher in LF-treated patients by 65 and 27%, respectively. Taken together, the data presented in this study revealed increased immune responsiveness in all patients treated with lactoferrin subjected to the thyroid surgery. This suggests that treatment with lactoferrin could constitute an effective protective measure against post-surgical complications.
Heparine is used as a therapeutic anticoagulant.Research carried out in the last years showed in both in vivo and in vitro experiments (also in men), that this is a pleiotropic substance with many diverse activities.Immunoregulatory properties of heparine, including immunosupressive and most of all anto-proliferative lead to create the theory of its possible use in sevral chronic inflamatory processes.First experiments seem to justify this opinion.
Advances in the treatment of transplant rejection, autoimmune disease, allergy, and other conditions of altered immunoregulation have come from our improved knowledge of the multi-faceted nature of lymphocyte activation, incorporating not merely antigen triggering of specific receptors, but a myriad of other accessory signals, all operating within a defined environmental (cytokine) milieu. The review below focuses on just one aspect of this, the ability to manipulate costimulatory signals, or regulatory signals, as a means to induce long-standing immune suppression. Emphasis is placed on the dominant suppression mediated following activation of any one of a number of regulatory signals as a potentially more rational approach to clinical therapy, as the redundancy in costimulatory signals suggests that blockade of any one of these may be unlikely to produce permanent unresponsiveness. The role of regulatory T cells, induced following antigen presentation in the presence of immunoregulatory signals, is also discussed.
Transplantation has emerged as an effective treatment for patients with end-stage organ failure. Current regimens of non-specific immunosuppressive drug treatment, which are needed life-long to prevent graft rejection, have numerous adverse side effects and increase the risk of opportunistic infections and malignancy. A major goal is to develop immunotherapeutic protocols that achieve specific tolerance. Such protocols would decrease and eventually eliminate the reliance on non-specific drug therapy. We showed that portal vein (pv) delivery of donor antigen prolongs the survival of vascularized and non-vascularized allo- and xeno-grafts, and that increased graft survival is associated with altered cytokine production and augmented expression of the molecule OX2. This review documents further evidence for a more general immunoregulatory role for the interactions of OX2 and its ligand, OX2L.
One of the great mysteries in modern immunology is how extraembryonic membranes escape rejection by maternal immune response, although they express paternal genes/antigenes which should stimulate allogenic recognition and rejection.Generally, two theories try to explain the pregnancy phenomenon.One of them emphasizes the role of immunosuppresive reactions in the protection of the fetus.On the contrary, the "immunotropism" theory insist on the importance of mother's immune antigens of the conceptus.Moreover, the last years abounded in discoveries on molecules regulating cell-cell interaction at the level of the initiation and effect or stage of the immune response.The best examples of such molecules could be extracellular matrix proteins, integrins, interleukins and various growth factors.The discussion of those molecules as regards their role in the protection of the fetus was the main aim of this article.
Immunoregulatory T cells play a key role in modifying the immune responses to self antigens, tumor antigens, and pathogenic organisms. This review summarizes recent data on naturally occurring CD4+ regulatory T cells that constitutively express CD25 (CD25+ Treg). We examine the markers that can be used to differentiate these cells from effector T cells, what is known about their mode of action in controlling the activity of effector T cells, the antigenic specificity of CD25+ Treg, and their ability to survive and to be selected in vivo. We also summarize specific information on the role of CD25+ Treg in controlling anti-tumor responses, an area were manipulation of this subset holds particular clinical promise.
Natural killer T (NKT) cells, which comprise a minor population of T cells in primary and secondary lymphoid organs, possess phenotypic characteristics of both NK and T cells. NKT cells respond to various external stimuli by an early burst of cytokines, including IL-4 and IFN-. Thus, a key immunoregulatory role has been attributed to them. Autoimmune diseases, especially type I diabetes (TID), may be caused by dysregulation of the immune system, which leads to hyporesponsiveness of regulatory T helper 2 (Th2) cells and promotion of autoimmune Th1 cells. Furthermore, several lines of evidence exist to support the notion that an NKT cell deficiency in individuals at risk of TID may be causal to TID. As a result, targeting NKT cells using immunotherapeutic agents may prove beneficial in the prevention or recurrence of TID. Indeed, our data demonstrate that stimulation of NKT cells with a specific ligand prevents the onset and recurrence of TID in non-obese diabetic (NOD) mice.
In the past few years it has been become increasingly clear that T cells capable of actively suppressing immune responses are thought to be in part responsible for the maintenance of peripheral self tolerance. In healthy rodents and humans, CD4+ T cells constitutively expressing the interleukin (IL)-2 receptor -chain (CD25) are able to exert such suppressive function in vitro and in vivo. Despite great efforts in our understanding of the biology of such immunoregulatory T cells, there are still certain points incompletely understood. Although some authors suggest that immunoregulatory cytokines such as IL-10 or transforming growth factor b are critical for the suppressive effect of these cells, this is controversial and the exact molecular nature and the targets of suppression are largely unknown. Thus far, until regulatory T cells can be used for diagnostic or therapeutic purposes many questions have to be answered. In this review we summarize the current knowledge on the function and properties of this T cell subset and discuss their potential role in human autoimmune or chronic inflammatory diseases.
The aim of this study was to analyze phenotypes of T cells activated by mitogen (PWM) and antigen (PPD) in the presence of FcR+ or FcR- monocytes. It was found that CD4+ and CD8+ lymphocytes are preferentially acitvated in the presence of different subpopulations. Expression of HLA-DR and CD25 on CD4+ lymphocytes was greater in cultures activated in the presence of FcR-. CD8+ lymphocytes were more efficiently activated (exprression of HLA-DR) when FcR+ monocytes were added to culture. In the presence of FcR+ monocytes an increased expression of CD45RA antigen on CD4+ cells was also observed. These data support our previous functional studies which showed that "suppressor" T cells of CD8+ phenotype are activated in the presence of FcR+ monocytes.
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