{"id":{"repo_id":"vt","oai_identifier":"oai:vtechworks.lib.vt.edu:10919/38934"},"canonical_url":"https://search.dev.ndltd.org/etd/vt/oai:vtechworks.lib.vt.edu:10919/38934","repository":{"repo_id":"vt","name":"Virginia Tech","base_url":"https://vtechworks.lib.vt.edu/oai/request"},"display":{"title":"Age-associated alterations in the immune system of normal and autoimmune-susceptible mice","abstract":"In 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.","abstract_html":"In 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&lt;sub&gt;H&lt;/sub&gt;1 and T&lt;sub&gt;H&lt;/sub&gt;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.","abstract_has_math":false,"creators":["Seth, Aruna"],"institution":"Virginia Tech","degree_name":"Ph. 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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."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph. 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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."],"dc:description.degree":["Ph. D."],"dc:format.medium":["BTD"],"dc:format.mimetype":["application/pdf"],"dc:identifier.other":["etd-07282008-135119"],"dc:identifier.uri":["http://hdl.handle.net/10919/38934"],"dc:language.iso":["en"],"dc:publisher":["Virginia Tech"],"dc:rights":["In Copyright"],"dc:rights.uri":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:title":["Age-associated alterations in the immune system of normal and autoimmune-susceptible mice"],"dc:type":["Dissertation"],"dc:type.dcmitype":["Text"],"thesis:degree_discipline":["Biology"],"thesis:degree_level":["doctoral"],"thesis:degree_name":["Ph. D."],"thesis:institution_name":["Virginia Polytechnic Institute and State University"]},"updated_at":"2026-07-22T22:20:40Z"}