Accelerated age-dependent decline in the T suppressor capacity of SJL mice

Tolerance induction with rabbit gamma-globulin was employed as a probe for age-dependent changes in suppressor capacity of SJL lymphoid cells. The tolerant state was assessed by loss of cooperative capacity and by infectious tolerance. The supply of precursor cells was assessed by thymectomy and by treatment with colchicine and cyclophosphamide, which have been reported to eliminate suppressor cells. Thymectomy, 16-18 days before tolerance induction, did not affect antibody response or tolerance inducibility; thymectomy, 33 days before tolerance induction, reduced both antibody response and tolerance inducibility. Colchicine, injected together with aggregate-freed rabbit gamma-globulin, inhibited tolerance induction partially in 35-day-old mice and completely in 106-day-old mice. Colchicine, given to younger mice, thymectomized 17 days before tolerance induction, prevented tolerance induction completely. A low dose of cyclophosphamide interfered with tolerance induction in older, but not in younger mice. A high dose of cyclophosphamide interfered with tolerance induction in thymus cells of younger and older mice. After thymectomy, there was a much more profound interference of a low dose of cyclophosphamide with tolerance induction. Results were discussed in terms of an age-dependent decline of thymus progenitors and of peripheral progenitors of suppressor cells.