Negative Regulation of Memory Phenotype CD8 T Cell Conversion by Adhesion and Degranulation-Promoting Adapter Protein

The Journal of Immunology : Official Journal of the American Association of Immunologists
Jessica K FiegeYoji Shimizu

Abstract

The maintenance of T cell repertoire diversity involves the entry of newly developed T cells, as well as the maintenance of memory T cells generated from previous infections. This balance depends on competition for a limited amount of homeostatic cytokines and interaction with self-peptide MHC class I. In the absence of prior infection, memory-like or memory phenotype (MP) CD8 T cells can arise from homeostatic cytokine exposure during neonatal lymphopenia. Aside from downstream cytokine signaling, little is known about the regulation of the conversion of naive CD8 T cells to MP CD8 T cells during acute lymphopenia. We have identified a novel negative regulatory role for adhesion and degranulation-promoting adapter protein (ADAP) in CD8 T cell function. We show that in the absence of ADAP, naive CD8 T cells exhibit a diminished response to stimulatory Ag, but an enhanced response to weak agonist-altered peptide ligands. ADAP-deficient mice exhibit more MP CD8 T cells that occur following thymic emigration and are largely T cell intrinsic. Naive ADAP-deficient CD8 T cells are hyperresponsive to lymphopenia in vivo and exhibit enhanced activation of STAT5 and homeostatic Ag-independent proliferation in response to IL-15. Our resu...Continue Reading

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Citations

Nov 20, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Vinay S MahajanShiv Pillai
Oct 22, 2019·Frontiers in Immunology·Jochen RudolphAnnegret Reinhold
Aug 16, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jessica K FiegeYoji Shimizu
Jan 13, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Naiqi YangHebin Liu
Aug 31, 2021·Frontiers in Immunology·Yael Dinur-SchejterPolina Stepensky

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