Self‐reactive T cell clones in a restricted population of interleukin‐2 receptor β⁺ cells expressing intermediate levels of the T cell receptor in the liver and other immune organs

Abstract

T cells expressing high levels of the T cell receptor (TCRhigh) differentiate in the major intrathymic pathway and then distribute to the peripheral immune organs, whereas T cells expressing intermediate levels of the TCR (TCRint) differentiate in both extrathymic pathways and an alternative intrathymic pathway and localize in unique sites, including the liver and thymic medulla. Since TCRint cells constitutively express interleukin-2 receptor beta-chain (IL-2R beta), two-color staining for CD3 (or TCR) and IL-2R beta clearly distinguished IL-2R beta+ CD3int (or TCRint) cells from IL-2R beta-, CD3high cells. CD3int cells may be considered to be primordial T cells based on their phenotype, morphology and other functional properties. In this study, using anti-V beta mAb in conjunction with the endogenous superantigen Mls, the distribution of self-reactive clones among T cells generated in all of the above pathways was investigated in mice. Self-reactive T cell clones were confined to IL-2R beta+, CD3int cells, in all of the organs tested. A significant proportion of self-reactive clones was never identified among CD3high cells in the thymus and peripheral immune organs in either young (8 week old) or old (50 week old) mice. Possibly reflecting their self-reactivity, CD3int cells, but neither NK cells nor CD3high cells had a potent cytotoxic effect against a syngeneic hepatoma in the presence of anti-CD3 mAb. These results raise the possibility that CD3int cells seen in the liver and thymus might belong to a similar primordial lineage of T cells, and that self-reactive clones are not generated through the major intrathymic pathway, but only through extrathymic pathways and an alternative intrathymic pathway.

Low level of mixing of partner cells seen in extrathymic T cells in the liver and intestine of parabiotic mice: its biological implication

“…Both subsets of CD3 int cells comprise self-reactive forbidden clones in the Mls system [25,26]. In a recent study, we proposed the possibility that NK1.1 + CD3 int cells in mice correspond to CD56 + T cells in humans while NK1.1 − CD3 int cells in mice correspond to CD57 + T cells in humans [27,28].…”

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

“…We previously showed the distinct functional properties of extrathymic T cells and thymus-derived T cells. Namely, extrathymic T cells (TCR int cells) eliminate abnormal self-cells (mainly self-antigens in the context of monomorphic major histocompatibility complex antigen) because of their autoreactivity (i.e., innate immunity), [21][22][23][24] whereas thymus-derived T cells (TCR high cells) interact with foreign antigens (mainly in the FIG. 7.…”

Intensive expansion of natural killer T cells in the early phase of hepatocyte regeneration after partial hepatectomy in mice and its association with sympathetic nerve activation

“…[1][2][3][4][5][6] In the case of mice, these extrathymic T cells are estimated to be interleukin 2R ␤-chain ϩ (IL-2R␤) intermediate CD3 (CD3 int ) cells, according to their constitutive expression of IL-2R␤ and the low density of TCR-CD3 complex (i.e., intermediate CD3 or CD3 int ) on the surface. Subsequently, we reported that IL-2R␤ ϩ CD3 int cells consist of both natural killer 1.1 ϩ (NK1.1 ϩ ) and NK1.1 Ϫ subsets at a ratio of approximately 1:1 in the liver.…”