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

2021 ◽  
Vol 11 ◽  
Author(s):  
Kalliopi Ioannidou ◽  
Daba-Rokhya Ndiaye ◽  
Alessandra Noto ◽  
Craig Fenwick ◽  
Sotirios P. Fortis ◽  
...  
Keyword(s):  
Tissue Level ◽  
Phenotypic Characterization ◽  
Surface Receptors ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Nuclear Factors ◽  
Quantitative Manner ◽  
Spatial Positioning

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.

A preliminary study on the characterization of follicular helper T (Tfh) cells in rheumatoid arthritis synovium

2014 ◽  
Vol 116 (3) ◽  
pp. 539-543 ◽  
Author(s):  
Yang Chu ◽  
Fengming Wang ◽  
Meng Zhou ◽  
Lujun Chen ◽  
Yahua Lu
Keyword(s):  
Rheumatoid Arthritis ◽  
Rheumatoid Arthritis Synovium ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Preliminary Study

scholarly journals The Function of T Follicular Helper Cells in the Autoimmune Liver Diseases

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Lin Li ◽  
Panyang Xu ◽  
Qi Zhou ◽  
Jiancheng Xu
Keyword(s):  
Liver Diseases ◽  
Humoral Response ◽  
B Cell Development ◽  
Autoantibody Production ◽  
Surface Receptors ◽  
Tfh Cells ◽  
Autoimmune Liver Diseases ◽  
Follicular Helper ◽  
Interleukin 21 ◽  
Cell Death Protein

T follicular helper (TFH) cells are recognized as a subtype of T cells that are involved in the germinal center formation and B cell development. When dysregulated, TFH cells may represent an important mechanism that contributes to a heightened humoral response and autoantibody production in autoimmune liver diseases (AILDs). TFH cells participate in the immune response associated with AILDs by expressing surface receptors such as programmed cell death protein-1, C-X-C motif chemokine receptor 5, and inducible T cell costimulators, as well as cytokines such as interleukin-21. TFH cells also downregulate chemokine (C-C motif) receptor 7 and promote the dysregulation of the T follicular regulatory/TFH axis. This review highlights the importance of TFH cells in AILDs.

Characterization of Human Follicular Helper T (TFH) Cells

2010 ◽  
Vol 135 ◽  
pp. S53
Author(s):  
Sang Taek Kim ◽  
Jin-Young Choi ◽  
Leah DiPlacido ◽  
Begona Lainez ◽  
Vivian Vlamakis ◽  
...  
Keyword(s):  
Tfh Cells ◽  
Follicular Helper

scholarly journals Phenotypic characterization of synovial tissue cells in situ in different types of synovitis

1983 ◽  
Vol 26 (11) ◽  
pp. 1321-1332 ◽  
Author(s):  
Staffan Lindblad ◽  
Lars Klareskog ◽  
Eva Hedfors ◽  
Urban Forsum ◽  
Christer Sundstrom
Keyword(s):  
Synovial Tissue ◽  
Phenotypic Characterization ◽  
Different Types ◽  
Tissue Cells

scholarly journals Acquisition of optimal TFH cell function is defined by specific molecular, positional, and TCR dynamic signatures

2021 ◽  
Vol 118 (18) ◽  
pp. e2016855118
Author(s):  
Kartika Padhan ◽  
Eirini Moysi ◽  
Alessandra Noto ◽  
Alexander Chassiakos ◽  
Khader Ghneim ◽  
...  
Keyword(s):  
B Cells ◽  
Synapse Formation ◽  
Cell Function ◽  
Immunological Synapse ◽  
Cell Receptor ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Molecular Determinants ◽  
Spatial Positioning ◽  
To Receive

The development of follicular helper CD4 T (TFH) cells is a dynamic process resulting in a heterogenous pool of TFH subsets. However, the cellular and molecular determinants of this heterogeneity and the possible mechanistic links between them is not clear. We found that human TFH differentiation is associated with significant changes in phenotypic, chemokine, functional, metabolic and transcriptional profile. Furthermore, this differentiation was associated with distinct positioning to follicular proliferating B cells. Single-cell T cell receptor (TCR) clonotype analysis indicated the transitioning toward PD-1hiCD57hi phenotype. Furthermore, the differentiation of TFH cells was associated with significant reduction in TCR level and drastic changes in immunological synapse formation. TFH synapse lacks a tight cSMAC (central supra molecular activation Cluster) but displays the TCR in peripheral microclusters, which are potentially advantageous in the ability of germinal center (GC) B cells to receive necessary help. Our data reveal significant aspects of human TFH heterogeneity and suggest that the PD-1hiCD57hi TFH cells, in particular, are endowed with distinctive programming and spatial positioning for optimal GC B cell help.

scholarly journals Human follicular CD4 T cell function is defined by specific molecular, positional and TCR dynamic signatures

2020 ◽  
Author(s):  
Kartika Padhan ◽  
Eirini Moysi ◽  
Alessandra Noto ◽  
Alexander Chassiakos ◽  
Khader Ghneim ◽  
...  
Keyword(s):  
T Cell ◽  
Synapse Formation ◽  
Cell Function ◽  
Immunological Synapse ◽  
Cell Receptor ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Tissue Organization ◽  
Spatial Positioning ◽  
And Function

AbstractThe orchestrated interaction between follicular helper CD4 T cells (TFH) and germinal center (GC) B cells is crucial for optimal humoral immunity. However, the regulatory mechanisms behind spatial distribution and function of TFH is not well understood. Here, we studied human TFH cells and found that transitioning to a CD57hi TFH status was associated with distinct positioning in the GC, phenotype, transcriptional signatures, function and downregulation of their T-cell receptor (TCR). Single cell TCR clonotype analysis indicated a unidirectional transition towards the CD57hi TFH status, which was marked with drastic changes in the nature of immunological synapse formation where peripheral microclusters become dominant. Lack of central supra molecular activation cluster (cSMAC) formation in TFH synapse was associated with enhanced ubiquitination/proteasome activity in these cells. Our data reveal significant aspects of the tissue organization and heterogeneity of follicular adaptive immunity and suggest that CD57hi TFH cells are endowed with distinctive programming and spatial positioning for optimal GC B cell help.One Sentence Summaryhuman TFH cell heterogeneity

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