Human thymic stromal lymphopoietin promotes dendritic cell–mediated CD4+ T cell homeostatic expansion


T cell homeostasis is a self-regulating process for maintaining the size of the peripheral T cell pool. Although dendritic cells (DCs) seem to be important in T cell homeostasis, the molecular regulation of DC-mediated T cell homeostasis is unknown. We show that human DCs activated by thymic stromal lymphopoietin (TSLP) induced a robust expansion of autologous CD4+ T cell populations, which depended on self peptide–major histocompatibility complex. The proliferating T cells adopted and maintained a central memory polyclonal phenotype and could differentiate into T helper type 1 or type 2 effector cells. These results, together with findings of TSLP expression in epithelial cells of mucosal lymphoid tissues and thymus, indicate that TSLP is involved in DC-mediated CD4+ T cell homeostasis.

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Figure 1: Naive CD4+ T cell proliferation and population expansion with autologous DCs activated by TSLP and other activators.
Figure 2: Cell surface markers characteristic of the CD4+ T cell population expanded by autologous TSLP-DCs.
Figure 3: Cytokine-producing capacity and responsiveness to TCR stimulation of CD4+ T cell populations expanded by autologous TSLP-DCs.
Figure 4: Central and effector memory CD4+ T cell proliferation and population expansion with autologous TSLP-DCs or Med-DCs.
Figure 5: Required factors and clonality of the CD4+ T cell population expanded by autologous TSLP-DCs.
Figure 6: T cell–DC interaction and DC survival.
Figure 7: Expression of human TSLP by cryptic epithelial cells of the tonsil and thymic epithelial cells of Hassal's corpuscles in the thymus.


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We thank B. Desai, S. Jungers, J. Shoemaker and J. Cupp for cell sorting; D. Wylie for assistance in preparation of the manuscript; and L.L. Lanier, J. Chen, B. Su, S. Ullrich, M.F. Wilkinson and Y.-H. Wang for critical reading and suggestions. DNAX Research Institute is supported by Schering-Plough.

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Correspondence to Yong-Jun Liu.

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