In vitro studies of the role of CD3+ and CD56+ cells in fetal liver cell alloreactivity.

Abstract

Previous functional studies have suggested that fetal liver cells (FLC) are capable of responding to allogeneic stimulation and have allostimulatory capacity by early in the second trimester. The present study was designed to analyze whether the allogenic response in human FLC is restricted to HLA class II expression and to evaluate the role of CD3+ cells (T cells) and CD56+ cells (natural killer cells) in the allogenic response. Mixed lymphocyte culture (MLC) experiments were performed on human FLC, at 14 to 18 gestational weeks, before and after depletion of HLA class II+ cells from the stimulator FLC pool (6-11 gestational weeks) and before and after depletion of CD3+ and CD56+ cells from the responder population. Depletion of HLA class II+ cells from the stimulator FLC pool resulted in a decreased response in 9 of 12 initially positive MLCs. CD3+ cell depletion from responder FLC resulted in a decreased response in four of seven experiments with peripheral blood lymphocytes as stimulators and in two of five experiments with FLC as stimulators. Depletion of CD56+ cells from responder FLC resulted in a decreased response in five of seven initially positive MLCs with peripheral blood lymphocytes as stimulators and two of five with FLC as stimulators. The results indicate that FLC are capable of alloresponsiveness when studied in MLC and that the response seems to be HLA class II dependent. Depletion of CD3+ or CD56+ cells led to a reduction in the MLC in a majority of the experiments. The question remains how these cells interact; it is likely that both cell types exhibit complementary effects in the early allogenic response.