title: Adhesion- and Degranulation-Promoting Adapter Protein Promotes CD8 T Cell Differentiation and Resident Memory Formation and Function during an Acute Infection.
abstract: During acute infections, naive Ag-specific CD8 T cells are activated and differentiate into effector T cells, most of which undergo contraction after pathogen clearance. A small population of CD8 T cells persists as memory to protect against future infections. We investigated the role of adhesion- and degranulation-promoting adapter protein (ADAP) in promoting CD8 T cell responses to a systemic infection. Naive Ag-specific CD8 T cells lacking ADAP exhibited a modest expansion defect early after Listeria monocytogenes or vesicular stomatitis virus infection but comparable cytolytic function at the peak of response. However, reduced numbers of ADAP-deficient CD8 T cells were present in the spleen after the peak of the response. ADAP deficiency resulted in a greater frequency of CD127(+) CD8 memory precursors in secondary lymphoid organs during the contraction phase. Reduced numbers of ADAP-deficient killer cell lectin-like receptor G1(-) CD8 resident memory T (TRM) cell precursors were present in a variety of nonlymphoid tissues at the peak of the immune response, and consequently the total numbers of ADAP-deficient TRM cells were reduced at memory time points. TRM cells that did form in the absence of ADAP were defective in effector molecule expression. ADAP-deficient TRM cells exhibited impaired effector function after Ag rechallenge, correlating with defects in their ability to form T cell-APC conjugates. However, ADAP-deficient TRM cells responded to TGF-β signals and recruited circulating memory CD8 T cells. Thus, ADAP regulates CD8 T cell differentiation events following acute pathogen challenge that are critical for the formation and selected functions of TRM cells in nonlymphoid tissues.
authors: Department of Laboratory Medicine and Pathology, Center for Immunology, Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455; and.
authors: Jessica K
authors: 0000-0002-4129-8742
authors: JK
authors: Fiege
authors: Department of Microbiology and Immunology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455.
authors: Lalit K
authors: 0000-0002-8597-3949
authors: LK
authors: Beura
authors: Department of Laboratory Medicine and Pathology, Center for Immunology, Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455; and.
authors: Brandon J
authors: 0000-0003-0922-7722
authors: BJ
authors: Burbach
authors: Department of Laboratory Medicine and Pathology, Center for Immunology, Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455; and shimi002@umn.edu.
authors: Yoji
authors: 0000-0001-9760-0288
authors: Y
authors: Shimizu
mesh_terms: D000208:Acute Disease; D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation; D016207:Cytokines / Q000096:biosynthesis; D007156:Immunologic Memory; D007239:Infections / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D054243:Vesicular Stomatitis / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; C491468:Fyb protein, mouse