THE SURVIVAL AND TURNOVER OF MATURE AND IMMATURE CD8 T-CELLS

The present investigation has examined the phenotype, survival and fat e of immature and mature CD8 T cells. CD4(-) CD8(+) 'single positive' thymocytes (a model for recent thymic emigrants) were Thy-1(+) CD45RC( -) RT6(-) before transfer to normal euthymic recipients, but changed p henotype within 7-10 days to become Thy-1(-) CD45RC(+) RT6(+)-the phen otype of mature resting CD8 T cells. Following transfer to athymic nud e recipients CD8 T cells from thoracic duct lymph of allotype-marked r ats increased 12-17-fold during the first 2 months. Proliferation occu rred in the complete absence of CD4 T cells and the donor CD8 T cells persisted [at 15-18% of peripheral blood lymphocytes (PBL)] for the li fe of the recipients. When combined with equal numbers of CD4 T cells, however, CD8 T cells occupied only 3-4% of PBL; in these animals CD4 T cells plateaued at 15-16% of PBL. The results suggested that CD8 T c ells competed poorly with rapidly dividing CD4 T cells for limited spa ce in a recirculating pool in which total T-cell numbers are homeostat ically regulated. Although able to proliferate and self-renew in athym ic nude recipients, when transferred to normal euthymic animals donor- derived mature CD8 T cells declined in number with time; their half-li fe was estimated to be 34 days. Similar studies with purified CD4(-) C D8(+) 'single positive' thymocytes gave a comparable half-life of 37 d ays. The results indicated that lifespan was not due to an ageing proc ess among CD8 T cells, but was rather a reflection of cell turnover de pendent on thymic output.