Consistent infiltration of thymus-derived T cells into the parenchymal space of the liver in normal mice

Abstract

We previously reported that extrathymic T cells (intermediate T-cell receptor cells [TCRIn a series of recent studies, 1-4 we have shown that the adult liver is one of the hematopoietic organs in mice, mainly producing extrathymic T cells (i.e., interleukin-2 receptor ␤ chain (IL-2R␤) ϩ intermediate T-cell receptor cells [TCR int cells]) and granulocytes from their own pre-existing precursor cells (i.e., c-kit ϩ Lin Ϫ stem cells). On the other hand, the bone marrow produces all hematopoietic cells, whereas the intestine (i.e., its cryptopatches) produces only extrathymic T cells. 5,6 Reflecting the above-mentioned situation, we have often encountered clusters of lymphoid and myeloid cells in the parenchymal space of the liver in normal or estrogentreated mice. 3 Because such clusters always contain c-kit ϩ Lin Ϫ cells and dividing cells (bromodeoxyuridine ϩ cells), 3,7 it is presumed that these clusters might be sites for the generation of extrathymic T cells and granulocytes in the liver. A similar phenomenon (i.e., c-kit ϩ Lin Ϫ cells giving rise to extrathymic T cells) occurs in the cryptopatches of the small intestine. 5,6 In the course of these studies, we observed that some lymphocytes also exist dispersely in the parenchymal space of the liver (including Glisson' s area) without cluster formation, even in normal adult mice. To determine the origin of these lymphocytes (namely, their being of extrathymic origin or of thymic origin), we intensively characterized the phenotype of cells before and after liver irrigation. Although intensive liver irrigation with physiological saline from the portal vein enriched extrathymic T cells (i.e., TCR int cells), thymus-

TNF-α-Induced Expression of Adhesion Molecules in the Liver Is Under the Control of TNFR1—Relevance for Concanavalin A-Induced Hepatitis

“…It is conceivable that this procedure also depleted the CD4 ϩ proportion of liver resident V␣14 NK T cells, which have been shown to be central for the onset of Con A-induced liver disease (40 -42). Hence, it seems likely that Con A-induced stimulation of local immune cells, i.e., NK T cells in concert with thymus derived T cells, which have been shown to be abundant in the parenchymal space (43), and liver resident macrophages are sufficient to induce hepatocellular damage. Recruitment of CD4 ϩ T cells from the circulation may then contribute to the elimination of harmful activated intrahepatic lymphocytes (i.e., T cells, NK T cells, or NK cells) (44).…”

Lymphocyte numbers and subsets in the human blood

“…This concept was supported by the finding that most of the liver lymphocytes cannot be removed by extensive perfusion of the liver. Further investigation of this population revealed that development and differentiation of these cells take place in the liver [72,73]. It has been proposed that the resident liver lymphocytes play a crucial role in coping with the immunological challenges and mediating tolerance by regular exposition to dietary antigens, foreign organisms, toxins and pathogens [70,74].…”

Antigen-Specific Primary Activation of CD8+ T Cells Within the Liver

“…It is therefore possible that naive T cells may contact hepatocytes in a similar way, as has been previously suggested by others for CTL (5). Likewise, a recent report suggested that lymphocytes recirculating via the blood enter the parenchymal space of the liver and, conversely, that extrathymic T cells generated in the parenchymal space migrate into the blood (33). Direct Ag presentation to T cells by hepatocytes expressing MHC class I and ICAM-1 (20), but not MHC class II, may explain why CD8 ϩ T cells are more prone than CD4 ϩ T cells to retention and death within the liver (32).…”