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*
Education and Research Centre and
Liver Unit, St. Vincent’s Hospital, Dublin, Ireland; and
Department of Medicine and Therapeutics, University College, Dublin, Ireland
The human liver contains significant numbers of T cells, NK cells,
and lymphocytes that coexpress T and NK cell receptors. To evaluate
their functional activities, we have compared the cytotoxic activities
and cytokines produced by normal adult hepatic
CD3+CD56- (T) cells,
CD3-CD56+ (NK) cells, and
CD3+CD56+ (natural T (NT)) cells. In
cytotoxicity assays using immunomagnetic bead-purified NK cell, T cell,
and NT cell subpopulations as effectors, 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 capable of redirected cytolysis of
P815 cells using Abs to CD3. Flow cytometric analysis of cytokine
production by fresh hepatic lymphocyte subsets activated by CD3
cross-linking or PMA and ionomycin stimulation indicated that NT cells
and T cells could produce IFN-
, TNF-
, IL-2, and/or IL-4, but
little or no IL-5, while NK cells produced IFN- and/or TNF- only.
The majority of NT cells produced inflammatory (Th1) cytokines only;
however, 
6% of all hepatic T cells, which included 5% of V24
TCR-bearing NT cells and 2% of 
TCR+ cells,
simultaneously produced IFN- 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 immunity, and possibly
peripheral deletion of autologous cells.
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