In Situ Characterization of Follicular Helper CD4 T Cells Using Multiplexed Imaging.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_0018D6BF0D49
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
In Situ Characterization of Follicular Helper CD4 T Cells Using Multiplexed Imaging.
Journal
Frontiers in immunology
Author(s)
Ioannidou K., Ndiaye D.R., Noto A., Fenwick C., Fortis S.P., Pantaleo G., Petrovas C., de Leval L.
ISSN
1664-3224 (Electronic)
ISSN-L
1664-3224
Publication state
Published
Issued date
2020
Peer-reviewed
Oui
Volume
11
Pages
607626
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Follicular helper CD4 T (Tfh) cells play an essential role in the formation of germinal centers (GCs), where mature B cells proliferate, differentiate, and provide long-term protective humoral responses. Despite the extensive phenotypic characterization and identification of human Tfh cell subsets, their spatial positioning at tissue level is not well understood. Here, we describe a quantitative multiplexed immunofluorescence approach allowing for the comprehensive in situ characterization of Tfh cells in human tonsils and lymph nodes (LNs) from individuals with angioimmunoblastic T-cell lymphoma (AITL). We have developed eight multiplexed panels comprising a spectrum of Tfh cell markers, like PD-1, CXCR5, and ICOS, along with transcription factors (Bcl6, Tbet, GATA3), to assess their expression, frequencies, spatial distribution and co-localization in a quantitative manner. Combined analysis of relevant markers revealed the presence of several Tfh cell subsets at tissue level based on the differential expression of surface receptors, nuclear factors as well as their distinct localization within the follicular areas. Interestingly, we found a considerable amount of tonsillar Tfh cells expressing high levels of the Th2 regulator GATA3. The co-expression of GATA3, CXCR5, and BCL6, points to an important role of GATA3 for the generation of effector human Tfh cells. Furthermore, our data revealed significantly different Tfh cell profile signatures between health and disease. Therefore, our imaging platform generates meaningful information for the in situ characterization of human Tfh cells and could provide the base for future studies aiming to a comprehensive understanding of Tfh cell tissue heterogeneity.
Keywords
angioimmunoblastic T-cell lymphoma, follicular helper T cells, germinal center, heterogeneity, multiplexed imaging, tonsil
Pubmed
Web of science
Open Access
Yes
Create date
01/03/2021 9:19
Last modification date
13/03/2021 7:22
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