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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Fiege, Jessica K. Shimizu, Yoji Burbach, Brandon J.
Description	Author Affiliation: Fiege JK ( Department of Laboratory Medicine and Pathology, Center for Immunology, Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455.); Burbach BJ ( Department of Laboratory Medicine and Pathology, Center for Immunology, Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455.); Shimizu Y ( Department of Laboratory Medicine and Pathology, Center for Immunology, Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455 shimi002@umn.edu.)
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 results indicate that ADAP dampens naive CD8 T cell responses to lymphopenia and IL-15, and they demonstrate a novel Ag-independent function for ADAP in the suppression of MP CD8 T cell generation.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	7
Volume Number	195
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adaptor Proteins, Signal Transducing Immunology Antigen-antibody Reactions Cd8-positive T-lymphocytes Interleukin-15 Lymphopenia Genetics Animals Cell Proliferation Enzyme Activation Immunologic Memory Mice Mice, Inbred C57bl Mice, Knockout Stat5 Transcription Factor Metabolism Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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