| Abstract: |
Because the deletion of self-reactive T cells is incomplete, thymic development of natural Foxp3<sup>+</sup>CD4<sup>+</sup> regulatory T cells (T<sub>reg</sub> cells) is required for preventing autoimmunity. However, the function of T cell antigen receptor (TCR) specificity in thymic T<sub>reg</sub> cell development remains controversial. To address this issue, we generated a transgenic line expressing a naturally occurring T<sub>reg</sub> cell-derived TCR. Unexpectedly, we found that efficient thymic T<sub>reg</sub> cell development occurred only when the antigen-specific T<sub>reg</sub> cell precursors were present at low clonal frequency (<1%) in a normal thymus. Using retroviral vectors and bone marrow chimeras, we observed similar activity with two other T<sub>reg</sub> cell-derived TCRs. Our data demonstrate that thymic T<sub>reg</sub> cell development is a 'TCR-instructive' process involving a niche that can be saturable at much lower clonal frequencies than is the niche for positive selection. |
| Keywords: |
controlled study; nonhuman; forkhead transcription factors; animal cell; mouse; animals; mice; mice, knockout; animal tissue; bone marrow cells; cell maturation; animal experiment; cell fate; cell differentiation; mice, transgenic; chimera; t lymphocyte receptor; regulatory t lymphocyte; antigen specificity; clonal variation; pre t lymphocyte; thymus; genes, t-cell receptor beta; receptors, antigen, t-cell; t-lymphocytes, regulatory; thymus gland
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