Thymically imprinted differential responsivity of naive CD4 T cells to IL2 results in a heterogeneity of both Treg induction and subsequent effector functioning

Pennock, N. D.; Qian, Y.; Ishihara, K.; Nakamura, Y.; Cross, E. W.; Sakaguchi, S.; White, J. T.

doi:10.1101/2023.10.08.561378

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bioRxiv · 10.1101/2023.10.08.561378

Thymically imprinted differential responsivity of naive CD4 T cells to IL2 results in a heterogeneity of both Treg induction and subsequent effector functioning

Pennock, N. D.·Qian, Y.·Ishihara, K.·Nakamura, Y.·Cross, E. W.·Sakaguchi, S.·White, J. T.

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Abstract

Thymic selection predisposes naive T cells to particular outcomes when challenged later with cognate antigen, whether the antigen is self or foreign. This suggests that there is an inherent heterogeneity of functioning among T cells within the naive population (both CD4 and CD8s), and that each T cell, as part of its thymic development, is given a certain programming which will affect its eventual fate decisions. In this project, we looked at the primary effects of this thymic imprinting on the conversion of naive CD4 T cells into Tregs. Further, using an induced-Treg-reporter system, we exam the impact of thymic imprinted heterogeneity on effector functionality and identity stability. We report that naive T cell differential responsivity to cytokines leads to the observed difference in Treg induction, and that the Tregs induced from T cells of different self-affinities maintain a heterogeneity of effector function and identity.

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Pennock, N. D., Qian, Y., Ishihara, K., Nakamura, Y., Cross, E. W., Sakaguchi, S., White, J. T.. 2023-10-10. Thymically imprinted differential responsivity of naive CD4 T cells to IL2 results in a heterogeneity of both Treg induction and subsequent effector functioning. https://doi.org/10.1101/2023.10.08.561378

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