Hepatology, April 2000, p. 1022-1024, Vol. 31, No. 4
Early research on T lymphocytes defined them as thymus-dependent cells (hence the designation "T") that express an immunoglobulin-like
two-chain antigen receptor (the TCR). The ligand-binding alpha and beta chains of this TCR do not possess signaling domains and transmit activation signals through a complex of associated transmembrane
proteins, collectively called CD3. These cells are key components of adaptive immunity, express very diverse receptors, and are capable of enormous clonal expansion in response to an antigenic challenge.
The relative expansion of specific T lymphocytes is part of the mechanism whereby a faster, more effective memory response is delivered on second encounter with an antigen.
In contrast to these T
cells, interest is growing in a diverse group of cells that express T-cell-like recognition structures but do not appear to show the massive clonal expansion and immunological memory of normal CD4+ and
CD8+ T cells. These cells include a population that shares properties of natural killer (NK) cells and alpha-beta T cells (termed NK-T cells) and several distinct subsets of cells that express
CD3-associated receptors associated with two distinct ligand-binding chains, gamma and delta. These cells may be collectively termed "natural T cells," because their effector functions are not
enhanced by earlier exposure to the same antigen (i.e., they do not show immunological memory). Although the molecular structure of the receptors on these cells is well understood, their biological
functions are much less clear. A report published in this journal, taken together with other information from the literature, suggests a unified model for the function of both the NK-like T cells, and
the gamma-delta T cells, which together comprise the natural T cell grouping.
The liver displays extraordinary powers of regeneration after injury, but the mechanism underlying this capacity is
not well understood. In this issue of HEPATOLOGY, Minagawa et al. report that the regeneration of the liver after partial hepatectomy is accompanied by a large increase in the numbers of T-cell
receptor-intermediate, mainly NK-like T cells. Further, they report that this increase is dependent on signaling through adrenergic receptors, because both the beta-blocker, propranolol, and the
alpha-blocker, phentolamine, inhibit the accumulation of these T cells. The lymphocytes isolated from regenerating liver displayed increased cytotoxic activity, which the investigators measured by using
both thymocytes and hepatocytes as targets.
Fig. 1. A hypothesis provoked by the work of Minagawa
et al., in which an adrenergic damage signal travels either
locally (via sympathetic neurons) or systemically (via secretion
of sympathetic hormones) and recruits natural T cells to the
damaged liver. These cells then participate in promoting cell
division and tissue repair. In the Figure, NK-T cell no. 1
is secreting growth factors, cell no. 2 is promoting the growth
and function of other NK-T cells, and cell no. 3 is delivering
a direct costimulatory signal through a receptor-ligand interaction
with the hepatocytes. Continued...