NATURAL-KILLER-CELL ONTOGENY IN THE ATHYMIC RAT - RELATIONSHIP BETWEEN FUNCTIONAL MATURATION AND ACQUIRED-RESISTANCE TO E1A ONCOGENE-EXPRESSING SARCOMA-CELLS

Newborn nude rats are NK cell deficient and highly susceptible to tumo r induction by NK-susceptible, E1A oncogene-expressing, BHK-21 sarcoma cells, whereas adults have normal NK activity and are tumor resistant , This model of NK cell-related tumor rejection was used to characteri ze age-related functional maturation of NK cells during nude rat ontog eny, Small numbers of cytolytic incompetent, NKR-P1(+) cells were dete cted in the spleens of newborns, During the first month of life, there was an age-related increase in the numbers of splenic NK cells, follo wed by a stepwise maturation in their cytolytic competence, Three func tional stages in NK cell cytolytic activity were apparent, A nonlytic newborn stage was followed by a transitional stage, during which absen t or relatively weak spontaneous cytolytic activity was augmented by p rolonged NK cell exposure to susceptible target cells, In the final st age, both spontaneous and augmented cytolytic activity increased towar d the adult level that was attained by 4 wk of age. The data suggest t he existence of a transient stage in NK cell ontogeny when triggering through the NKR-P1 molecule is functionally immature, and confirm the importance of a cytolytic competent, NK cell response for nude rat rej ection of E1A oncogene-expressing tumor cells.