The human liver contains multiple populations of NK cells, T cells, and CD3(+)CD56(+) natural T cells with distinct cytotoxic activities and Th1, Th2, and Th0 cytokine secretion patterns

The human liver contains significant numbers of T cells, NK cells, and lymp hocytes that coexpress T and NK cell receptors, To evaluate their functiona l activities, we have compared the cytotoxic activities and cytokines produ ced by normal adult hepatic CD3(+)CD56(-) (T) cells, CD3(-)CD56(+) (NK) cel ls, and CD3(+)CD5(+) (natural T (NT)) cells. In cytotoxicity assays using i mmunomagnetic bead-purified NK cell, T cell, and NT cell. subpopulations as effecters, fresh hepatic NK cells lysed K562 targets, while NT cells could be induced to do so by culturing with IL-2, Both NT and T cells were capab le of redirected cytolysis of P815 cells using Abs to CD3, Flow cytometric analysis of cytokine production by fresh hepatic lymphocyte subsets activat ed by CD3 crosslinking or PPc ZA and ionomycin stimulation indicated that N T cells and T cells could produce IFN-gamma, TNF-alpha, IL-2, and/or IL-4, but little or no IL-5, while NK cells produced IFN-gamma and/or TNF-alpha o nly. The majority of NT cells produced inflammatory (Th1) cytokines only; h owever, similar to 6% of all hepatic T cells, which included 5% of V alpha 24 TCR-bearing NT cells and 2% of gamma delta TCR+ cells, simultaneously pr oduced IFN-gamma and IL-4, The existence of such large numbers of cytotoxic lymphocytes with multiple effector functions suggests that the liver is an important site of innate immune responses, early regulation of adaptive im munity, and possibly peripheral deletion of autologous cells.