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Nat Commun. 2017 Nov 13;8(1):1473. doi: 10.1038/s41467-017-01728-5.

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

Author information

1
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
2
Bioinformatics Core Facility, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
3
Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA.
4
Genetech Research Institute, Colombo, 00800, Sri Lanka.
5
Department of Zoology and Environment Sciences, Science Faculty, University of Colombo, Colombo, 00700, Sri Lanka.
6
North Colombo Teaching Hospital, Ragama, 11010, Sri Lanka.
7
National Institute of Infectious Diseases, Gothatuwa, Angoda, 10620, Sri Lanka.
8
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA. alex@lji.org.
9
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, 92037, USA. bpeters@lji.org.

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.

PMID:
29133794
PMCID:
PMC5684192
DOI:
10.1038/s41467-017-01728-5
[Indexed for MEDLINE]
Free PMC Article

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