Evaluation of presence and functional activity of potentially self-reactive T cells in aged mice.

Abstract

Autoimmunity is known to increase in aging. A possible factor could be an alteration in the T cell repertoire with advancing age. Antibodies to the variable region of the beta chain of the TCR activate T cells and can serve as probes for analysis of the T cell repertoire. We have used V beta 3 and V beta 17a antibodies to determine the presence and functionality of normally deleted T cells bearing potentially self-reactive TCR in peripheral lymphoid tissue and blood from aged (SJL/J x BALB/c) F1, LAF1 and BALB/c mice. Although an occasional 20- to 24-month-old mouse exhibited V beta 3+ or V beta 17a+ T cells in their lymph nodes or peripheral blood lymphocytes (PBL) slightly above the range for normal young mice of these I-E+ strains, there was no striking 'escape' from the normal thymic deletion process. However, responsiveness to anti-V beta 3 and anti-V beta 17a was slightly higher in aged, and particularly in aged thymectomized (TX), than in young mice. This was in contrast to proliferative responses to stimulation with antibody to the normally expressed V beta 8, which were lower in the lymph nodes from aged than from young mice. The PBL of some 30- to 36-month-old mice were also examined. Enhanced numbers of 'forbidden' V beta bearing T cells were seen more frequently at this age. In spite of the age-related decrease in overall CD4/CD8 T cell ratios in all organs, the mice with relatively high V beta 17a + T cells exhibited proportionally more CD4+ cells in that V beta population. We conclude that the 'forbidden' T cells that respond to anti-V beta stimulation in the 20- to 24-month-old mice are most likely to extra-thymic origin, since they were more readily detectable in aged TX mice. Potentially self-reactive Cd4 (and CD8) single-positive T cells were detectable in PBL only in very aged (30-36 months old) euthymic mice.