INDUCTION OF TCR-GAMMA-DELTA(-DERIVED HEPATOCYTE CLONE() CELLS FROM THYMOCYTES STIMULATED BY A FETAL LIVER)

We have previously reported that a fetal liver-derived hepatocyte clon e, FHC-4D2, can support hematopoiesis in vitro. Here, we show that fet al thymocytes (FT) or adult thymocytes (AT) proliferate on the monolay er of FHC-4D2 cells in the presence of rIL-2. Fresh thymocytes contain ed few TCR-gamma delta(+) cells (<4% for FT and <1% for AT); significa nt numbers of TCR-gamma delta(+) cells were detected (2-11% for FT and 15-33% for AT) after the coculture with FHC-4D2 and rIL-2. Although F T-derived TCR-gamma delta(+) cells predominantly used the V gamma 5 ch ain, the major population in AT-derived TCR-gamma delta(+) cells used V gamma 1, V gamma 4, or V gamma 7 chains. Both FT- and AT-derived TCR -gamma delta(+) cells killed FcR-bearing target cells when incubated w ith anti-TCR-gamma delta Ab. Half of FT-derived TCR-gamma delta(+) cel ls were CD4(-)CD8 alpha(+)8 beta(-); the rest were CD4(-)CD8 alpha(-)8 beta(-). AT-derived TCR-gamma delta(+) cells expressed neither CD4 no r CD8 molecules. Separation of thymocytes from FHC-4D2 cells with a me mbrane filter reduced the proliferative response by two- to threefold. Taken together, these results demonstrate that a fetal hepatocyte clo ne supports thymocytes to develop preferentially into TCR-gamma delta( +) cells in cooperation with rIL-2 through cell-cell contact, that the repertoire and the phenotype of induced TCR-gamma delta(+) cells are determined by the age of the mice, and that hepatocytes might thus pla y an active role in T lymphopoiesis in the fetal liver.