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. / Ph. D.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/38934 |
| Date | 28 July 2008 |
| Creators | Seth, Aruna |
| Contributors | Biology, Nagarkatti, Prakash S., Nagarkatti, Mitzi, Stout, Ernest R., Schurig, Gerhardt, Elgert, Klaus |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Language | English |
| Detected Language | English |
| Type | Dissertation, Text |
| Format | xiii, 179 leaves, BTD, application/pdf, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
| Relation | OCLC# 23716230, LD5655.V856_1990.S475.pdf |
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