Investigating aire deficiency in the context of human autoimmune disease associated HLA molecules

dc.contributor.advisorForsthuber, Thomas G.
dc.contributor.authorNalawade, Saisha
dc.contributor.committeeMemberCardona, Astrid E.
dc.contributor.committeeMemberGuentzel, M. Neal
dc.date.accessioned2024-02-12T18:28:01Z
dc.date.available2024-02-12T18:28:01Z
dc.date.issued2012
dc.descriptionThis item is available only to currently enrolled UTSA students, faculty or staff. To download, navigate to Log In in the top right-hand corner of this screen, then select Log in with my UTSA ID.
dc.description.abstractAutoimmunity arises as a result of the immune system initiating an attack on self-molecules. Autoreactive T cells are one of the key mediators in many autoimmune diseases such as multiple sclerosis (MS) and rheumatoid arthritis (RA). Central tolerance induced in the thymus is the key mechanism involved in eliminating these autoreactive T cells that recognize self antigens. The autoimmune regulator (AIRE) gene regulates central tolerance by mediating ectopic transcription of self antigens in the thymus. Deficiency of AIRE in humans can break the central tolerance causing a multi-organ autoimmune disorder known as autoimmune polyendocrinopathy syndrome (APS I). Aire deficient mice <italic>(aire-/-)<italic> can develop spontaneous autoimmune disease characterized by multi-organ specific lymphocytic infiltrates. The association between HLA-DR2 and DR4 molecules to MS and also RA has been established. The aim of the study was to investigate aire deficiency in mice in the context of the human autoimmune disease associated MHC alleles; HLA-DR2 and HLA-DR4. The detection of T cell infiltrates in liver and pancreas and autoantibody production against the gastric tissue in a few older <italic>aire-/-<italic> DR2 and DR4 transgenic mice suggested that these mice develop mild spontaneous autoimmunity. Further we also observed that mild autoimmunity could be triggered in the <italic>aire-/-<italic> transgenic DR2 and DR4 mice by abrogation of T regulatory cell function through the use of blocking antibody against CTLA-4 and CD25. We also observed that aire deficiency appeared to have a mild effect on promoting experimental autoimmune encephalomyelitis (EAE), particularly in the DR2 transgenic background. Also, Treg inactivation after EAE induction in <italic>aire-/-<italic> DR2 transgenic mice showed a mild disease enhancing effect in female mice. Thus, the study revealed that aire deficiency in the context of HLA-DR2 and DR4 molecules elicited a mild spontaneous autoimmune phenotype.
dc.description.departmentIntegrative Biology
dc.format.extent53 pages
dc.format.mimetypeapplication/pdf
dc.identifier.isbn9781267843241
dc.identifier.urihttps://hdl.handle.net/20.500.12588/4657
dc.languageen
dc.subjectBiotechnology
dc.subject.classificationMolecular biology
dc.subject.classificationImmunology
dc.subject.classificationbiology
dc.titleInvestigating aire deficiency in the context of human autoimmune disease associated HLA molecules
dc.typeThesis
dc.type.dcmiText
dcterms.accessRightspq_closed
thesis.degree.departmentIntegrative Biology
thesis.degree.grantorUniversity of Texas at San Antonio
thesis.degree.levelMasters
thesis.degree.nameMaster of Science

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