AUTOIMMUNE-DISEASE AS A CONSEQUENCE OF DEVELOPMENTAL ABNORMALITY OF AT-CELL SUBPOPULATION

Neonatal thymectomy (NTx), especially around day 3 after birth, causes various organ-specific autoimmune diseases in mice. This report shows that: (n) T cells expressing the interleukin 2 receptor oc chains (CD 25) ontogenically begin to appear in the normal periphery immediately after day 3, rapidly increasing within 2 wk to nearly adult levels (si milar to 10% of CD3(+) cells, especially of CD4(+) cells); (b) NTx on day 3 eliminates CD25(+) T cells G-om the periphery for several days; inoculation immediately after NTx of CD25(+) splenic T cells from syng eneic non-Tx adult mice prevents autoimmune development, whereas inocu lation of CD25(-) T cells even at a larger dose does not; and furtherm ore, (c) similar autoimmune diseases can be produced in adult athymic nu/nu mice by inoculating either spleen cell suspensions from 3-d-old euthymic nu/+ mice or CD25(+) cell-depleted spleen cell suspensions fr om older, even l-yr-old, nu/+ mice. The CD25(-) populations from neona tes or adults are also similar ill the profile of cytokine formation. These: results, taken together, indicate that one aspect of peripheral self-tolerance is maintained by CD25(+) T cells that sustain potentia lly pathogenic self-reactive T cells in a CD25(-) dormant state; the t hymic production of the former is developmentally programmed to begin on day 3 after birth in mice. Thus, NTx on day 3 can, at least transie ntly, eliminate/reduce the autoimmune-preventive CD25(+) T cells, ther eby leading to activation of the self-reactive T cells that have been produced before NTx.