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V beta gene repertoires in aging mice
R González-Quintial1, A N Theofilopoulos
1Department of Immunology, Scripps Research Institute, La Jolla, CA 92037.
Journal of Immunology (Baltimore, Md. : 1950)
|July 1, 1992
Summary
Aging does not impair T cell selection in the thymus or lead to T cell repertoire instability. Despite thymic involution, T cell repertoires remain stable, with no evidence of abnormal clone expansion or peripheral leakage in aged mice.
Area of Science:
- Immunology
- T cell biology
- Aging research
Background:
- Thymic involution, a hallmark of aging, involves a reduction in thymus cellularity.
- Potential consequences include defects in T cell selection and repertoire instability.
Purpose of the Study:
- To investigate the impact of aging and thymic involution on intrathymic T cell selection.
- To assess clonal stability and peripheral T cell receptor (TCR) repertoire integrity with age.
Main Methods:
- Comparison of V beta gene transcript levels in thymic and splenic T cells from young, adult, and old mice.
- Analysis across different Mls and MHC haplotypes (C57BL/6, BALB/c, DBA/2).
- Assessment in irradiated and bone marrow-reconstituted old mice to evaluate peripheral T cell behavior.
Main Results:
- Unselected thymic V beta repertoires remained stable throughout life, irrespective of reduced thymic cellularity in aged mice.
- Splenic CD4 and CD8 V beta repertoires showed no significant age-related alterations.
- No leakage of endogenous superantigen-reactive V beta clones to the periphery was observed with age.
Conclusions:
- Aging and thymic involution do not appear to cause defects in intrathymic T cell selection or clonal instability.
- The T cell repertoire is robust and maintained throughout life, even under conditions of thymic atrophy.
- Exploration revealed novel reactivities between V beta segments and staphylococcal toxins.