Development of autoreactivity and changes of T cell repertoire in different strains of aging mice.

Physiological changes with increasing age are generally accompanied by disorders of immunity, including autoaggression which can be seen in some syngeneic host-versus-graft reactions provoked when responder and stimulator cells are of different ages. The magnitude of the response, however, varies with the strain of mice. Footpad injection of irradiated spleen cells from 1-year-old, but not from 2-month-old, BALB/c mice (H-2d) into syngeneic young mice evoked popliteal lymph node-swelling, but this was not the case in DBA/2 (H-2d) mice. Therefore, the generation of autoreactivity was thought to be closely related to the change of T cell repertoire with age in the former strain of mice. At around 1 year of age, when only a small reduction in T cell number was observed and when a slight increase in CD8+ T cells in the periphery caused the CD4/CD8 ratio to be lower than in young mice, the proportion of V beta 8+ cells in BALB/c mice started to increase, increasing from 16% in the young to 27% in 2-year-old mice (P < 0.01). On the other hand, V beta 6+ T cells remained at the same level as in young mice throughout life. The increasing fraction of V beta 8+ T cells was characterized by a low density of T cell receptors (TcR) and it was more conspicuous in the spleen than in the peripheral blood in mice more than 1 year of age. A shift to a TcR-low population in V beta 8+, T cells was followed in a few months by a shift in V beta 6+ T cells. Although both the change of T cell repertoire and development of autoaggression may be parameters of aging, no direct correlation was demonstrated between them in experiments with cross-hybrids and recombinant inbred strains of BALB/c and DBA/2 mice. Probably, the two parameters are genetically and independently controlled. All the data taken together indicate that T cells undergo V beta-TcR-restricted changes during their life history, depending on their genetic background.