Virginia Tech
Age-associated alterations in the immune system of normal and autoimmune-susceptible mice
Abstract
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.
Degree
thesis:*- Name thesis:degree_name
- Ph. D.
- Level thesis:degree_level
- doctoral
- Discipline thesis:degree_discipline
- Biology
- Department dc:contributor.department
- Biology
- Grantor dc:publisher
- Virginia Tech
- Year dc:date.issued
- 1990
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Seth, Aruna
- Chair dc:contributor.committeechair
-
- Nagarkatti, Prakash S.
- Committee members dc:contributor.committeemember
-
- Nagarkatti, Mitzi
- Stout, Ernest R.
- Schurig, Gerhardt
- Elgert, Klaus
Rights
dc:rights- Statement dc:rights
-
- In Copyright
- Licence dc:rights.uri
- Language dc:language.iso
- en
Identifiers
dc:identifier.*- Dc Identifier Other
- etd-07282008-135119
- OAI identifier oai:identifier
- oai:vtechworks.lib.vt.edu:10919/38934