PD-1 Controls Tonic Signaling and Lymphopenia-Induced Proliferation of T Lymphocytes

Frontiers in Immunology
Kristofor K EllestadColin C Anderson

Abstract

Recovery of the T lymphocyte compartment within a lymphopenic host by lymphopenia-induced proliferation (LIP) is regulated by inter- and intraclonal competition for limited resources, including homeostatic cytokines and peptide:MHC (pMHC) complexes with which the TCR can interact at least weakly to yield a tonic signal. Importantly, the process of LIP can synergize with other factors that promote T cell activation to drive inflammatory disease. While reconstitution of the lymphoid compartment of immune deficient Rag(-/-) mice by transfer of wild-type hematopoietic stem cells (HSC) does not generally result in an overt disease phenotype, transfer of HSC deficient in expression of the co-inhibitory molecule PD-1 results in severe systemic autoimmunity driven by newly generated T cells that emerge from the thymus into the periphery and undergo LIP. Importantly, autoimmunity does not appear to depend on a response to exogenous (i.e., gut flora-derived) antigens. PD-1 is well known to be upregulated during T cell activation in response to cognate antigens, but it is unclear whether PD-1 has a role in controlling LIP of T cells in the absence of cognate antigen, i.e., in response to tonic pMHC. We examined whether PD-1 controls LIP o...Continue Reading

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Citations

Oct 8, 2019·Scandinavian Journal of Immunology·Tibor BakacsColin C Anderson
May 3, 2019·Theoretical Biology & Medical Modelling·Csaba KerepesiTamás Szabados
Jul 9, 2020·Scandinavian Journal of Immunology·Donald R Forsdyke
Aug 14, 2019·Immunological Reviews·Darienne R MyersJeroen P Roose
Aug 1, 2020·Frontiers in Immunology·Alexandra TsitsiklisEllen A Robey
Oct 14, 2018·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Annette KünkeleMichael C Jensen
May 1, 2021·International Journal of Molecular Sciences·Ting-Ting Sheu, Bor-Luen Chiang

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Methods Mentioned

BETA
transgenic
flow cytometry

Software Mentioned

Treestar
FlowJo
Graphpad Prism

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