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Immunoregulatory Activity (immunoregulatory + activity)
Selected AbstractsImmunoregulatory Activity, Biochemistry, and Phylogeny of Ovine Uterine SerpinAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2001MORGAN R. PELTIER PROBLEM: During pregnancy, the endometrium of the ewe secretes a progesterone-induced member of the serpin superfamily of serine proteinase inhibitors called ovine uterine serpin (OvUS) that has immunosuppressive properties. METHOD: Review of the literature. RESULTS AND CONCLUSIONS: OvUS inhibits a wide variety of immune responses, including mixed lymphocyte reaction, mitogen-stimulated lymphocyte proliferation, and T cell-dependent antibody production. Recent data have suggested that OvUS functions by inhibiting protein kinase C and interleukin-2-mediated events. OvUS and similar genes present in cattle and pigs diverged from other serpins prior to the divergence of artiodactyls. Since this time, the serpins have apparently undergone adaptive evolution that has led to a conformational state and biological functions distinct from prototypical serpins. Thus, it is likely that these proteins have an important role in the reproductive biology of Artiodactyla. Several lines of evidence suggest that, in sheep, OvUS functions to mediate the immunosuppressive effects of progesterone and prevent immunological rejection of the fetal allograft. [source] The Critical Role of IL-12p40 in Initiating, Enhancing, and Perpetuating Pathogenic Events in Murine Experimental Autoimmune NeuritisBRAIN PATHOLOGY, Issue 4 2002Lei Bao Interleukin 12 (IL-12) is a proinflammatory cytokine with important immunoregulatory activities and is critical in determining the differentiation and generation of Th1 cells. For the present study, we investigated the role of endogenous IL-12 in the pathogenesis of experimental autoimmune neuritis (EAN), which is a CD4+ T-cell mediated autoimmune inflammatory disease of the peripheral nervous system. EAN is used as an animal model for Guillain-Barré syndrome of humans. Here, EAN was established in IL-12 p40 deficient mutant (IL-12 -/- ) C57BL/6 mice by immunization with P0 peptide 180,199, a purified component of peripheral nerve myelin, and Freund's complete adjuvant. In these IL-12 -/- mice the onset of clinical disease was delayed, and the incidence and severity of EAN were significantly reduced compared to that in wild-type mice. The former group's clinical manifestations were associated with less P0-peptide 180,199 induced secretion of interferon-, (IFN-,) by splenocytes in vitro and low production of anti-P0-peptide 180,199 IgG2b antibodies in serum. Fewer IFN-, and TNF-, producing cells, but more cells secreting IL-4, were found in sciatic nerve sections from IL-12 -/- mice, consistent with impaired Th1 functions and response. However, the IL-12 deficiency appeared not to affect P0 peptide 180,199-specific T-cell proliferation. These results indicate that IL-12 has a major role in the initiation, enhancement and perpetuation of pathogenic events in EAN by promoting a Th1 cell-mediated immune response and suppressing the Th2 response. This information augments consideration of IL-12 as a therapeutic target in Guillain-Barré syndrome and other T-cell-mediated autoimmune diseases. [source] Tamm-Horsfall protein: a multilayered defence molecule against urinary tract infectionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2005M. D. Säemann Abstract Urinary tract infection (UTI) is the most common nonepidemic bacterial infection in humans, representing a constant danger for the host. Both innate and adaptive components of the immune system as well as stromal cells including bladder epithelium are involved in the prevention and clearance of UTI. However, the particular properties of the urogenital tract, which does not comprise typical physical barriers like a mucus or ciliated epithelium, necessitate soluble mediators with potent immunomodulatory capabilities. One candidate molecule capable of both mediating direct antimicrobial activity and alerting immune cells is the evolutionary conserved Tamm-Horsfall protein (THP). Tamm-Horsfall protein is exclusively produced by the kidney in the distal loop of Henle; however, its definite physiological function remains elusive. Mounting evidence indicates that beyond a mere direct antimicrobial activity, THP exerts potent immunoregulatory activity. Furthermore, the genetic ablation of the THP gene leads to severe infection and lethal pyelonephritis in an experimental model of UTI. Recent data are provided demonstrating that THP links the innate immune response with specific THP-directed cell-mediated immunity. In light of these novel findings we discuss the particular role of THP as a specialized defence molecule. We propose an integrated model of protective mechanisms against UTI where THP acts by two principle nonmutually exclusive mechanisms involving the capture of potentially dangerous microbes and the ability of this peculiar glycoprotein to induce robust protective immune responses against uropathogenic bacteria. [source] Novel CD8+ Treg suppress EAE by TGF-,- and IFN-,-dependent mechanismsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2009Mei-Ling Chen Abstract Although CD8+ Treg-mediated suppression has been described, CD8+ Treg remain poorly characterized. Here we identify a novel subset of CD8+ Treg that express latency-associated peptide (LAP) on their cell surface (CD8+LAP+ cells) and exhibit regulatory activity in vitro and in vivo. Only a small fraction of CD8+LAP+ cells express Foxp3 or CD25, although the expression levels of Foxp3 for these cells are higher than their LAP, counterparts. In addition to TGF-,, CD8+LAP+ cells produce IFN-,, and these cells suppress EAE that is dependent on both TGF-, and IFN-,. In an adoptive co-transfer model, CD8+LAP+ cells suppress myelin oligodendrocyte glycoprotein (MOG)-specific immune responses by inducing or expanding Foxp3+ cells and by inhibiting proliferation and IFN-, production in vivo. Furthermore, in vivo neutralization of IFN-, and studies with IFN-,-deficient mice demonstrate an important role for IFN-, production in the function of CD8+LAP+ cells. Our findings identify the underlying mechanisms that account for the immunoregulatory activity of CD8+ T cells and suggest that induction or amplification of CD8+LAP+ cells may be a therapeutic strategy to help control autoimmune processes. [source] Interleukin-21 is a T-helper cytokine that regulates humoral immunity and cell-mediated anti-tumour responsesIMMUNOLOGY, Issue 2 2004Pallavur V. Sivakumar Summary Cytokines and their receptors represent key targets for therapeutic intervention. Ligands are being used to supplement cell numbers that become depleted as a result of disease (organ failure, infection) or subsequent disease treatments (i.e. chemotherapy). Conversely, the inhibition of target cell binding by cytokines is an established strategy for abrogating pathologic cellular activities common to many immunological diseases. Considerable effort in biomedical research is being focused on the cytokine families that play a dominant role in regulating immunity and then prioritizing each member for its therapeutic potential. Currently, the interleukin-2 (IL-2) family of cytokines is widely recognized for its central involvement in controlling lymphocyte function and is the most explored for medical utility. Collectively, these proteins (or their antagonists) are either marketed drugs or have received advanced testing for an impressive array of indications including cancer, infectious disease, transplantation, inflammation and allergic asthma. Here we review the current understanding of IL-21, the most recent member of this cytokine family to be discovered. As will be discussed, IL-21 shares many of the same attributes as its relatives in that it has broad immunoregulatory activity and can modulate both humoral and cell-mediated responses. Its ability to stimulate durable anti-tumour responses in mice defines one therapeutic indication that merits clinical development. [source] Regional Immunity of the EyeACTA OPHTHALMOLOGICA, Issue 3 2010Manabu Mochizuki Abstract. This article reviews molecular mechanism of intraocular inflammation in animal models and in humans, and the immunological defence system of the eye with particular attention to ocular pigment epithelium. In experimental autoimmune uveitis (EAU), T lymphocytes, particularly CD4+ T lymphocytes, play a central role in its immunopathogenic mechanisms. In humans, activated CD4+ T cells also play a central role in the immunopathogenic mechanisms. This notion is demonstrated in two human diseases: one is Vogt,Koyanagi,Harada disease, and the other is human T-cell leukemia virus type 1 (HTLV-1) uveitis. Activated CD4+ T cells infiltrating the eye are harmful to vision-related cells and tissues in the eye and cause sight-threatening conditions. However, the eye has regional defence systems to protect itself from these harmful activated T cells. We focus on ocular pigment epithelium (PE) and demonstrate immunoregulatory activity of iris PE and retinal PE. Iris PE suppresses activated CD4+ T cells by cell-to-cell contact with a crucial role played by B7-2 molecule on iris PE and CTLA4 on T cells. The actual immunosuppressive factor being membrane bound TGF-,. In contrast, retinal PE suppresses activated CD4+ T cells by soluble factors, such as soluble TGF-, and thrombospondin 1. In addition to the direct T-cell suppression by ocular PE, ocular PE has the capacity to promote activated T cells to regulatory T cells and use them as a tool to amplify the immune down regulation in the eye. The molecular mechanisms of generation of T regulatory cells by iris PE and retinal PE is also discussed. [source] | ||||||||||