PROMOTION OF FETAL LIVER-CELL ENGRAFTMENT IN IRRADIATED MICE BY ACTIVATED T-LYMPHOCYTES

The promoting effect of T lymphocytes on hematopoietic cell engraftment was studied in lethally irradiated CBA and Balb/c mice by transplantation of either liver cells from Balb/c fetuses (FLBalb) or FLBalb plus Balb/c T lymphocytes (TBalb). Additional groups of lethally irradiated CBA and Balb/c mice received T lymphocytes only, either from CBA (TCBA) or from Balb/c donors. Injection of TBalb lymphocytes had no effect on the splenic indices (SI) nor on the numbers of colony-forming units in the spleens (CFU-S) of FLBalb-transplanted Balb/c mice on day 7. In contrast, it increased these parameters in the CBA recipients of FLBalb in a T cell-dose dependent fashion and it stimulated their hematologic recovery on day 20 following irradiation. TCBA and TBalb lymphocytes transplanted alone did not induce CFU-S in syngeneic recipients but promoted the development of CFU-S of endogenous origin in the histoincompatible mice. The development of CFU-S was enhanced in the FLBalb-transplanted Balb/c mice by injection of TBalb lymphocytes previously stimulated in vitro with irradiated CBA splenocytes, phorbol myristate acetate (PMA), phytohemagglutinin (PHA) or concanavalin A (conA). This effect was associated with an increased survival rate of the recipient mice. Daily injections for 6 days of a culture supernatant from a mixture of TBalb cells and irradiated CBA splenocytes, but not from irradiated CBA splenocytes alone, promoted the development of CFU-S in FLBalb-transplanted Balb/c recipients. However, the supernatant of stimulated TBalb cells was less efficient than the stimulated T cells themselves. These data indicate that T lymphocytes may enhance hematopoietic cell engraftment in irradiated allogeneic mice on cell-to-cell contact with the allogeneic host cells, resulting in donor T cell activation and lymphokine release.