Figure 2
Figure 2. Normal thymic T-cell maturation and export. T-cell development requires the import of a bone marrow-derived progenitor population (yellow symbols) via the blood circulation into the thymus cortex. During optimal thymus function in healthy young persons, TN cells proliferate strongly in the cortex in response to signals provided by cTECs (eg, interleukin-7, stem cell factor, chemokines). The subsequent DP stage of thymocyte maturation is subject to thymic-positive selection. In parallel to their migration to the medulla, DP cells differentiate into SP thymocytes, which are subjected to the negative selection process. pGE in Aire-expressing mTECs plays a crucial role in clonal deletion. The mature T cells (white symbols) are exported as RTE via blood circulation to peripheral lymphoid tissues. The magnitude of thymic export can be assessed by TREC analysis. This approach is based on the fact that thymocytes undergo 2 sequential rounds of TCR rearrangements that form 2 families of TREC as byproducts. TCRB rearrangement in TN cells forms several DβJβ TREC species (●), which are diluted among the expanding cell population before the TCRAD is rearranged in DP cells, which generates sjTREC (○). Thymic export can be measured via determination of the sj/β ratio. This signature for RTE indicates the extent of TN cell proliferation, which is in turn a key determinant for the extent of thymic export. The sj/β ratio remains independently of peripheral cell division at approximately 100:1 in young persons. DC indicates dendritic cells; and sj/β, calculated ratio between sjTREC and DβJβTREC.

Normal thymic T-cell maturation and export. T-cell development requires the import of a bone marrow-derived progenitor population (yellow symbols) via the blood circulation into the thymus cortex. During optimal thymus function in healthy young persons, TN cells proliferate strongly in the cortex in response to signals provided by cTECs (eg, interleukin-7, stem cell factor, chemokines). The subsequent DP stage of thymocyte maturation is subject to thymic-positive selection. In parallel to their migration to the medulla, DP cells differentiate into SP thymocytes, which are subjected to the negative selection process. pGE in Aire-expressing mTECs plays a crucial role in clonal deletion. The mature T cells (white symbols) are exported as RTE via blood circulation to peripheral lymphoid tissues. The magnitude of thymic export can be assessed by TREC analysis. This approach is based on the fact that thymocytes undergo 2 sequential rounds of TCR rearrangements that form 2 families of TREC as byproducts. TCRB rearrangement in TN cells forms several DβJβ TREC species (●), which are diluted among the expanding cell population before the TCRAD is rearranged in DP cells, which generates sjTREC (○). Thymic export can be measured via determination of the sj/β ratio. This signature for RTE indicates the extent of TN cell proliferation, which is in turn a key determinant for the extent of thymic export. The sj/β ratio remains independently of peripheral cell division at approximately 100:1 in young persons. DC indicates dendritic cells; and sj/β, calculated ratio between sjTREC and DβJβTREC.

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