Cutting edge: CD69 interference with sphingosine-1-phosphate receptor function regulates peripheral T cell retention

Laura K Mackay; Asolina Braun; Bethany L Macleod; Nicholas Collins; Christina Tebartz; Sammy Bedoui; Francis R Carbone; Thomas Gebhardt

doi:10.4049/jimmunol.1402256

Cutting edge: CD69 interference with sphingosine-1-phosphate receptor function regulates peripheral T cell retention

J Immunol. 2015 Mar 1;194(5):2059-63. doi: 10.4049/jimmunol.1402256. Epub 2015 Jan 26.

Authors

Laura K Mackay¹, Asolina Braun², Bethany L Macleod², Nicholas Collins², Christina Tebartz², Sammy Bedoui², Francis R Carbone², Thomas Gebhardt¹

Affiliations

¹ Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia [email protected] [email protected].
² Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia.

PMID: 25624457
DOI: 10.4049/jimmunol.1402256

Abstract

Tissue-resident memory T cells provide local immune protection in barrier tissues, such as skin and mucosa. However, the molecular mechanisms controlling effector T cell retention and subsequent memory formation in those locations are not fully understood. In this study, we analyzed the role of CD69, an early leukocyte activation marker, in regulating effector T cell egress from peripheral tissues. We provide evidence that CD69 surface expression by skin-infiltrating CD8 T cells can be regulated at multiple levels, including local Ag stimulation and signaling through type I IFNRs, and it coincides with the transcriptional downregulation of the sphingosine-1-phosphate receptor S1P1. Importantly, we demonstrate that expression of CD69, by interfering with sphingosine-1-phosphate receptor function, is a critical determinant of prolonged T cell retention and local memory formation. Our results define an important step in the generation of long-lived adaptive immune memory at body surfaces.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptive Immunity
Animals
Antigens, CD / genetics
Antigens, CD / immunology*
Antigens, Differentiation, T-Lymphocyte / genetics
Antigens, Differentiation, T-Lymphocyte / immunology*
Antigens, Viral / genetics
Antigens, Viral / immunology*
CD8-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / pathology
CD8-Positive T-Lymphocytes / virology
Coculture Techniques
Dendritic Cells / immunology
Dendritic Cells / pathology
Dendritic Cells / virology
Female
Gene Expression Regulation
Herpesvirus 1, Human / genetics
Herpesvirus 1, Human / immunology
Immunologic Memory*
Immunophenotyping
Interferon Type I / genetics
Interferon Type I / immunology
Lectins, C-Type / genetics
Lectins, C-Type / immunology*
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, Lysosphingolipid / genetics
Receptors, Lysosphingolipid / immunology*
Signal Transduction
Skin / immunology
Skin / pathology
Skin / virology

Substances

Antigens, CD
Antigens, Differentiation, T-Lymphocyte
Antigens, Viral
CD69 antigen
Interferon Type I
Lectins, C-Type
Receptors, Lysosphingolipid