Development of cell-mediated lympholysis in human foetal blood lymphocytes

White cells from pure foetal blood obtained by fetoscopy, or from the cord at birth, were sensitized in mixed lymphocyte culture with irradiated adult peripheral blood lymphocytes. After 6-8 days of culture they were assayed in a standard 4-hr 51Cr-release cytotoxicity assay (CML) using lymphoblastoid cell targets from the stimulator cell donor. The age of the foetuses ranged from 15-22 weeks of gestation. Third-party target cells and adult blood served as controls. The mean cytotoxic responses of cord (11 donors) and adult (10 donors) blood lymphocytes were not significantly different and had similar kinetics. Foetal lymphocytes (25 donors) displayed a wide range of reactivity with half, scattered throughout the age range, totally negative and a further 23% with marginal responses. Definite cytotoxicity was found in the remainder, but not before the 18th week; these responses were evenly distributed in the range 18-22 weeks. Third-party responses were never more than one-quarter of the specific cytotoxicity. It was shown that the negative and very weak responses were almost certainly not due to technical factors. It is concluded that the majority of human foetuses in the range 15-22 weeks, though capable of giving clear mixed lymphocyte reactions, cannot develop full effector function as measured by the CML assay.