Physiological responses of extrathymic T cells in the liver

The liver has been found to be one of the important hematopoietic organs ev en after birth. Namely, adult liver still comprises c-kit(+) stem cells and gives rise to extrathymic T cells, natural killer (NK) cells, and even gra nulocytes. Extrathymic T cells generated in the liver of mice are intermedi ate T-cell receptor (TCRint) cells, including the NK1.1(+)TCR(int) (i.e. NK T cells) and NK 1.1-TCRint subsets. Although extrathymic T cells are few in number in, youth, they gradually increase in number with aging. Even in yo uth, the number and function of extrathymic T cells are elevated under cond itions of stress, infection, malignancy pregnancy, autoimmune disease, chro nic graft-versus-host diseases, etc. Under these conditions, the mainstream of T-cell differentiation in the thymus, which produces conventional T cel ls, is rather suppressed. Since extrathymic T cells comprise self-reactive forbidden clones and mediate cytotoxicity against abnormal self-cells (e.g malignant tumor cells, microbially infected hepatocytes, and regenerating h epatocytes), they are beneficial for the elimination of such cells. However , overactivation or continuous activation of extrathymic T cells might be h armful and responsible for the onset of autoimmune diseases. We finally pro pose the possibility that switching of the immune system from the thymus to the liver might be regulated by the autonomic nervous system as well as by cytokines.