Search for: [Abstract = "It is well known that immunization via the digestive tract or nasal mucosa may induce a strong local response and simultaneously leads to a state of profound immunosuppression in the periphery. For many years, the skin was considered to be an organ where immune responses such as contact hypersensitivity \(CHS\) were easily induced. However, skin as a site for the induction of tolerance has received very little attention. Experiments performed at the Department of Medical Biology at Jagiellonian University School of Medicine showed that, indeed, epicutaneous \(EC\) application of protein antigens resulted in the induction of T regulatory cells \(Treg\) which were able to inhibit murine Th1 CD4\+ \-mediated contact sensitivity to a TNP\-coupled protein. EC immunization with a protein antigen prior to active contact sensitization was shown to be mediated by TCRαβ\+ CD4\+ CD8\+, in an antigen non\-specific manner. The mechanism of skin\-induced suppression relies on the action of the anti\-inflammatory cytokine TGF\-β. Recently it was shown that EC application of a protein antigen reduced inflammatory responses and decreased disease incidence in two different experimental models\: experimental autoimmune encephalomyelitis \(EAE\) and collagen induced arthritis \(CIA\). Further work employing allogeneic skin grafts showed that EC immunization with a protein antigen delayed graft rejection in mice. The effector and regulating mechanisms of CHS mediated by Th1 CD4\+ lymphocytes are well known, which may contribute to the development of new methods of contact skin inflammation treatment.In this dissertation, it was investigated whether the EC immunization with a DNP\-coupled protein antigen can suppress Tc1 CD8\+\-mediated contact hypersensitivity in BALB\/c mice. We have found that EC immunization with DNP\-conjugated bovine serum albumin \(DNP\-BSA\) prior to sensitization with 0.5% dinitrofluorobenzene \(DNFB\) did indeed suppress Tc1 CD8\+\-mediated CHS in vivo when compared with positive control. The observed reduction of ear swelling was correlating with the depression of vascular permeability, ear weight, IFN\-γ concentration and MPO activity in ear homogenates. These results were confirmed by an in vitro model, where EC deposition of a protein antigen suppressed proliferation of Tef cells. It was also shown that DNP\-BSA application prior to sensitization with DNFB significantly inhibited production of pro\-inflammatory IFN\-γ, IL\-12 and TNF\-α.In a further experiment it was determined that the optimal dose of EC\-applied DNP\-BSA which could suppress CHS ranges between 100 and 3 µg of antigen \/ mouse and that the state of unresponsiveness declined with time and lasted for around three weeks."]

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