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J Immunol. 2016 Sep 15;197(6):2079-89. doi: 10.4049/jimmunol.1501805. Epub 2016 Aug 12.

Adhesion- and Degranulation-Promoting Adapter Protein Promotes CD8 T Cell Differentiation and Resident Memory Formation and Function during an Acute Infection.

Author information

1
Department of Laboratory Medicine and Pathology, Center for Immunology, Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455; and.
2
Department of Microbiology and Immunology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455.
3
Department of Laboratory Medicine and Pathology, Center for Immunology, Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455; and shimi002@umn.edu.

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.

PMID:
27521337
PMCID:
PMC5010998
DOI:
10.4049/jimmunol.1501805
[Indexed for MEDLINE]
Free PMC Article

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