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 (TCR^high) differentiate in the major intrathymic pathway and then distribute to the peripheral immune organs, whereas T cells expressing intermediate levels of the TCR (TCR^int) differentiate in both extrathymic pathways and an alternative intrathymic pathway and localize in unique sites, including the liver and thymic medulla. Since TCR^int cells constitutively express interleukin‐2 receptor β‐chain (IL‐2R), two‐color staining for CD3 (or TCR) and IL‐2Rβ clearly distinguished IL‐2RßT⁺ CD3^int (or TCR^int) cells from IL‐2Rβ⁻, CD3^high cells. CD3^int cells may be considered to be primordial T cells based on their phenotype, morphology and other functional properties. In this study, using anti‐Vβ 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‐2Rβ⁺, CD^int cells, in all of the organs tested. A significant proportion of self‐reactive clones was never identified among CD3^high 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, CD3^int cells, but neither NK cells nor CD3^high cells had a potent cytotoxic effect against a syngeneic hepatoma in the presence of anti‐CD3 mAb. These results raise the possibility that CD3^int 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.