Intraclonal competition limits the fate determination of regulatory T cells in the thymus

作者: Jhoanne L Bautista , Chan-Wang J Lio , Stephanie K Lathrop , Katherine Forbush , Yuqiong Liang

DOI: 10.1038/NI.1739

关键词: FOXP3ReceptorChimera (genetics)Cell biologyCellular differentiationAutoimmunityBiologyCytotoxic T cellAntigenT-cell receptorImmunology

摘要: Because the deletion of self-reactive T cells is incomplete, thymic development natural Foxp3+CD4+ regulatory (Treg cells) required for preventing autoimmunity. However, function cell antigen receptor (TCR) specificity in Treg remains controversial. To address this issue, we generated a transgenic line expressing naturally occurring cell-derived TCR. Unexpectedly, found that efficient occurred only when antigen-specific precursors were present at low clonal frequency (o1%) normal thymus. Using retroviral vectors and bone marrow chimeras, observed similar activity with two other TCRs. Our data demonstrate 'TCR-instructive' process involving niche can be saturable much lower frequencies than positive selection.

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