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The role of IL-17 in kidney transplantation - abstract Naive CD4+ T-lymphocytes (Thp) can develop into Th17 line in the presence of TGF- and IL-6. Th17 cells are characterized by expression of Ror- t and by production of interleukin-17 (IL-17). It is secreted as a glycoprotein homodimer. Binding to IL-17 receptor (IL-17R), which is present in all cell types, stimulates the production of proinflammatory cytokines and chemokines. The ratio of Th17: Treg in the graft showing signs of rejection is higher than in the graft without rejection. The presence of IL-17 in a culture of proximal tubular epithelial cells (PTEC) stimulates the production of IL-6, IL-8, MCP-1 and C3 complement component. Simultaneous action of IL-17 and CD40L synergistically increases the production of IL-6, IL-8 and RANTES. Signaling from the receptor on the surface of PTEC associated with its increased expression is effected via the src kinase and MAP kinase, and probably leads to the transcription factor NF- B. In rat models of transplantation, the IL-17 appears in allografts on the second day after surgery, the level rises until the fifth day, then decreases and disappears before the death of the animal. IL-17 is not detectable in isografts and negative controls. It appears before the IFN- , which had been considered a trigger of...

Mesenchymal stem cells (MSC) are extensively studied mainly due to their feasible clinical application. Therapeutic potential of MSC consists not only of the ability to differentiate into mesenchymal cells, ectodermal and endodermal cell lines, but primarily in their immunomodulatory functions. Due to their effect on immune cells, MSC promote the shift of the inflammatory immune response to antiinflammatory. The ability to suppress inflammation, together with their differentiation potential and antiapoptotic potential on the surrounding cells makes MSC a promising tool for treating serious diseases. This work discusses the effect of MSC on the individual cells of the immune system. It focuses on the description of the effect of MSC in four model cases. These are an experimental autoimmune encephalomyelitis, myocardial infarction, diabetes mellitus and skin graft transplantation. The knowledge of the mechanisms of the interactions between MSC and the cells of the immune system, together with the understanding the effect of specific conditions on MSC is essential for their use in clinical therapy. Keywords: mesenchymal stem cells, immunomodulation, autoimmune diseases, transplantation

Experimental models of a transfer of stem cells for therapeutic purposes Abstract Stem cell therapy currently represents a standard procedure of treating a wide variety of hereditary diseases and serious injuries. Development of the most suitable way of transfer of stem cells into the patient body remains very important question concerning this type of therapy. In our experiments we used nanofiber scaffolds for stem cell cultivation and their subsequent transfer. These nanofibers were prepared by the original needleless electrospun NanospiderTM technology. Allogeneic cornea or skin graft were transplanted from B6 mice to BALB/c mice. The grafts were covered by a nanofibrous scaffold with cultivated stem cells. Stem cells were stained by an imunofluorescent dye to enable us to monitore their migration from nanofibers into tissues and consequent distribution in the body and characterize changes of this distribution in the time. The methods of ELISA and PCR were used to confirm that mesenchymal stem cells support the production of antiinflammatory cytokines IL-4 and IL-10 and contribute to inhibition of production of proinflammatory cytokines IL-1, IFNγ and inducible nitric oxide synthase. We confirmed an important beneficial role of nanofiber scaffolds in transplantation of mesenchymal stem cells. Nanofiber...

Genetic influence of Trypanosoma brucei brucei infection in mice The African trypanosomes are zoonotic parasites transmitted by Tse-Tse flies. Two of the three subspecies, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, cause sleeping sickness in humans whereas the third subspecies, Trypanosoma brucei brucei is not infective to humans. These parasites are members of Kinetoplastida. Trypanosomes are extracellular parasite witch have complex life cycles involving both insect and mammalian hosts. African trypanosomes after infection penetrate mainly vascularized organs and get into brain where cause serious pathology. Parasite can manipulate with immune system of mammal host in wide spectrum of interactions witch are not clearly understood so far. Discovering of a new immune mechanisms, whitch participite in reaction on african trypanosomes, can reveal some general characteristics of immune system. The results of these studies can help to prepare effective drugs and vaccines against this disease. The best way to observe pathological manifestation and genetical analysis is study on animal models . Study on suitable animal model to find genes which are responsible for control of immune response to T. brucei can help us to find homologous genes in humans. It was found that immune responces to...

Cancer treatment with polymer-bound cytostatic drugs and its potentiation through immunomodulation Poly[N-2-(hydroxypropyl)-methacrylamide] (PHPMA) is a synthetic water soluble and biocompatible polymer which can be used as a carrier of a cytostatic drug and an antibody as a targeting moiety. The antibody ensures the site-specific delivery of the conjugate. Nevertheless, even polymeric conjugates without any tumor-specific targeting moiety are passively accumulated within solid tumors via so called Enhanced Permeability and Retention (EPR) effect, in case that their molecular wight is at least 40 kDa. Antibody-targeted polymeric drugs have been shown previously to have a cytostatic activity in vitro and an antitumor activity in vivo. Since treatment of cancer diseases in practice is far from such ideal conditions and many tumors have no strictly specific marker suitable for targeted therapy, upgrading of the treatment efficacy represents the major challenge. One of the possible ways how to improve insufficient chemotherapy outcome can be using of a combination of polymer-bound cytostatic drug and potent immunomodulation able to induce a robust anti-cancer immune response. In this study, we have used B cell leukemia BCL1 as an experimental tumor model. BCL1 cells express surface IgM with an unique...

5 Induction of the immune response against HPV16-associated tumours with experimental vaccines The E6/E7 oncoproteins of human papillomaviruses are expressed in most trans- formed cells of cervical carcinoma and, therefore, are attractive targets for T cell-mediated immunotherapy. We have investigated the capacity of vaccines based on E7 oncoprotein- derived peptides to induce cellular immune responses and their therapeutic potential for treatment of minimal residual disease after surgery in a murine experimental model mi- micking human HPV16-associated carcinomas. We compared the effect of E749-57 peptide (RAHYNIVTF) exhibiting immunodominant epitope recognized by cytotoxic T lymphocy- tes with E744-62 peptide (QAEPDRAHYNIVTFCCKCD = 8Q) exhibiting CTL, TH and B- cell epitopes. Immune responses were compared in healthy mice and in mice after surgery or chemotherapy of tumours with ifosfamide derivative CBM-4A. Cellular immune re- sponses were monitored in spleen cells of C57BL/6 mice using ELISPOT-IFN-γ and 51 Cr- release assay. Flow cytometry was used for the detection of CD4+ , CD8+ , CD4+ CD25+ , Gr-1+ CD11b+ and CD3+ NK1.1+ populations. Vaccination with 8Q peptide and synthetic CpG oligodeoxynucleotide as adjuvant induced stronger antitumour immune responses than immunodominant CTL epitope alone in both...