Unique phenotypes and clonal expansions of human CD4 effector memory T cells re-expressing CD45RA

Yuan Tian, Mariana Babor, Jerome Lane, Veronique Schulten, Veena S. Patil, Grégory Seumois, Sandy L. Rosales, Zheng Fu, Gaelle Picarda, Julie Burel, Jose Zapardiel-Gonzalo, Rashika N. Tennekoon, Aruna D. Silva, Sunil Premawansa, Gayani Premawansa, Ananda Wijewickrama, Jason A. Greenbaum, Pandurangan Vijayanand, Daniela Weiskopf, Alessandro Sette () and Bjoern Peters ()
Additional contact information
Yuan Tian: La Jolla Institute for Allergy and Immunology
Mariana Babor: La Jolla Institute for Allergy and Immunology
Jerome Lane: La Jolla Institute for Allergy and Immunology
Veronique Schulten: La Jolla Institute for Allergy and Immunology
Veena S. Patil: La Jolla Institute for Allergy and Immunology
Grégory Seumois: La Jolla Institute for Allergy and Immunology
Sandy L. Rosales: La Jolla Institute for Allergy and Immunology
Zheng Fu: La Jolla Institute for Allergy and Immunology
Gaelle Picarda: La Jolla Institute for Allergy and Immunology
Julie Burel: La Jolla Institute for Allergy and Immunology
Jose Zapardiel-Gonzalo: La Jolla Institute for Allergy and Immunology
Rashika N. Tennekoon: La Jolla Institute for Allergy and Immunology
Aruna D. Silva: La Jolla Institute for Allergy and Immunology
Sunil Premawansa: Science Faculty, University of Colombo
Gayani Premawansa: North Colombo Teaching Hospital
Ananda Wijewickrama: National Institute of Infectious Diseases
Jason A. Greenbaum: La Jolla Institute for Allergy and Immunology
Pandurangan Vijayanand: La Jolla Institute for Allergy and Immunology
Daniela Weiskopf: La Jolla Institute for Allergy and Immunology
Alessandro Sette: La Jolla Institute for Allergy and Immunology
Bjoern Peters: La Jolla Institute for Allergy and Immunology

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: Abstract The expression of CD45RA is generally associated with naive T cells. However, a subset of effector memory T cells re-expresses CD45RA (termed TEMRA) after antigenic stimulation with unknown molecular characteristics and functions. CD4 TEMRA cells have been implicated in protective immunity against pathogens such as dengue virus (DENV). Here we show that not only the frequency but also the phenotype of CD4 TEMRA cells are heterogeneous between individuals. These cells can be subdivided into two major subsets based on the expression of the adhesion G protein-coupled receptor GPR56, and GPR56+ TEMRA cells display a transcriptional and proteomic program with cytotoxic features that is distinct from effector memory T cells. Moreover, GPR56+ TEMRA cells have higher levels of clonal expansion and contain the majority of virus-specific TEMRA cells. Overall, this study reveals the heterogeneity of CD4 TEMRA cells and provides insights into T-cell responses against DENV and other viral pathogens.

Date: 2017
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DOI: 10.1038/s41467-017-01728-5

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