Age-associated alterations in the immune system of normal and autoimmune-susceptible mice

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dc.contributor.authorSeth, Arunaen
dc.contributor.committeechairNagarkatti, Prakash S.en
dc.contributor.committeememberNagarkatti, Mitzien
dc.contributor.committeememberStout, Ernest R.en
dc.contributor.committeememberSchurig, Gerhardten
dc.contributor.committeememberElgert, Klausen
dc.contributor.departmentBiologyen
dc.date.accessioned2014-03-14T21:16:43Zen
dc.date.adate2008-07-28en
dc.date.available2014-03-14T21:16:43Zen
dc.date.issued1990en
dc.date.rdate2008-07-28en
dc.date.sdate2008-07-28en
dc.description.abstractIn this study, the effect of aging on various cells of the immune system was investigated. The two experimental models used were normal young (1-2 months) and old (22-24 months) DBA/2 mice and autoimmune-susceptible young (1-2 months) and old (5-6 months) MRL-Ipr/Ipr (Ipr) mice. Autoreactive T cell clones isolated from DBA/2 mice were used to study the age-induced differential responses of syngeneic T cells and B cells. These cell interactions were found to be greatly diminished in old DBA/2 mice, and this appeared to be due to an intrinsic defect in the cells from old mice. A decreased syngeneic mixed lymphocyte reaction (SMLR) was also found to be associated with these defects in T-T and T-B interactions. The decreased SMLR was due to a reduction in the production of interleukin-1 by macrophages from old mice. In the Ipr mice, age-induced alterations in the cell surface characteristics of the abnormal T cells that accumulate in the lymph nodes were studied. The double-negative T cells from the lymph nodes of old Ipr mice were found to express a cell surface marker, J11d, that is normally present only on immature T cells in the thymus. Furthermore, the number of double-negative J11d⁺ T cells also increased in the thymus of old Ipr mice. Autoreactive T cell clones isolated from DBA/2 and /pr mice exhibited the properties of both T<sub>H</sub>1 and T<sub>H</sub>2 subsets as the clones secreted IL-2, IL-4 and IFN-γ, and activated both B cells and macrophages. The current study indicates that with increasing age, the autoreactive T cell-induced immunoregulation is disturbed, which may account for reduced immune responsiveness to foreign antigens and increased susceptibility to autoimmune diseases.en
dc.description.degreePh. D.en
dc.format.extentxiii, 179 leavesen
dc.format.mediumBTDen
dc.format.mimetypeapplication/pdfen
dc.identifier.otheretd-07282008-135119en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-07282008-135119/en
dc.identifier.urihttp://hdl.handle.net/10919/38934en
dc.language.isoenen
dc.publisherVirginia Techen
dc.relation.haspartLD5655.V856_1990.S475.pdfen
dc.relation.isformatofOCLC# 23716230en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subject.lccLD5655.V856 1990.S475en
dc.subject.lcshAge factors in diseaseen
dc.subject.lcshImmune system -- Researchen
dc.titleAge-associated alterations in the immune system of normal and autoimmune-susceptible miceen
dc.typeDissertationen
dc.type.dcmitypeTexten
thesis.degree.disciplineBiologyen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePh. D.en

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