Tolerance of self induced in thymus organ culture

Abstract

F liver protein occurs in serum at low concentration, and therefore induces tolerance of self only in T cells. T cells which mature in cultured thymus lobes in the absence of this protein become reactive towards it but can be prevented from doing so by exposure to the protein while in culture. The threshold of tolerance induction for this soluble antigen is estimated in this way at approximately 1 microgram/ml, which is slightly less than the threshold of response of primed T cells in a proliferation assay. Freshly isolated thymocytes do not display reactivity to self-F protein, indicating that T cells normally become tolerant while still within the thymus.

Peripheral T cell tolerance as a tumor escape mechanism: deletion of CD4+ T cells specific for a monoclonal immunoglobulin idiotype secreted by a plasmacytoma

“…Our results contrast with previous findings that T cell tolerance to antigens like F liver protein (10-8-10-' M, [45]) hen egg lysozyme (-1 ng/ml, [46,47]) and human insulin (< 1 ng/ml, [48]) requires relatively low concentrations of antigen as measured by functional assays. However, the mechanism of T cell tolerance in these experiments is basically unknown.…”

Altered Th1/Th2 balance associated with the immunosuppressive/protective effect of the H‐2Ab allele on the response to allo‐4‐hydroxyphenylpyruvate dioxygenase

“…The affinities recorded here may seem at first sight surprising, since that of the responder H-2Ak molecule is so low in comparison with those of the neutral H-2Ad and H-2A5 molecules, and with the negative selection threshold of -lo-* M [18]. We think it likely that the non-responder status of these neutral molecules may reflect the creation of holes in the repertoire [12], and that low site-occupancy is not incompatible with their mediating negative selection.…”

Dose‐dependent T cell tolerance to an immunodominant self peptide

“…In another Tg mouse model for human carcinoembryonic antigen (CEA), Tg animals were tolerant to the CEA at serum concentrations S lo-"' M [32]. However, in an in vitro model using cultured thymus lobes, the threshold of tolerance induction to F liver protein was determined at about 1 pg/ml (lo-* M ) [33]. A similar concentration of chicken ovalbumin peptide ( 5 …”