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Cytokine-Independent Detection of Antigen-Specific Germinal Center T Follicular Helper Cells in Immunized Nonhuman Primates Using a Live Cell Activation-Induced Marker Technique.

作者信息

Havenar-Daughton Colin, Reiss Samantha M, Carnathan Diane G, Wu Jennifer E, Kendric Kayla, Torrents de la Peña Alba, Kasturi Sudhir Pai, Dan Jennifer M, Bothwell Marcella, Sanders Rogier W, Pulendran Bali, Silvestri Guido, Crotty Shane

机构信息

Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, La Jolla, CA 92037;

Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;

出版信息

J Immunol. 2016 Aug 1;197(3):994-1002. doi: 10.4049/jimmunol.1600320. Epub 2016 Jun 22.


DOI:10.4049/jimmunol.1600320
PMID:27335502
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4955744/
Abstract

A range of current candidate AIDS vaccine regimens are focused on generating protective HIV-neutralizing Ab responses. Many of these efforts rely on the rhesus macaque animal model. Understanding how protective Ab responses develop and how to increase their efficacy are both major knowledge gaps. Germinal centers (GCs) are the engines of Ab affinity maturation. GC T follicular helper (Tfh) CD4 T cells are required for GCs. Studying vaccine-specific GC Tfh cells after protein immunizations has been challenging, as Ag-specific GC Tfh cells are difficult to identify by conventional intracellular cytokine staining. Cytokine production by GC Tfh cells may be intrinsically limited in comparison with other Th effector cells, as the biological role of a GC Tfh cell is to provide help to individual B cells within the GC, rather than secreting large amounts of cytokines bathing a tissue. To test this idea, we developed a cytokine-independent method to identify Ag-specific GC Tfh cells. RNA sequencing was performed using TCR-stimulated GC Tfh cells to identify candidate markers. Validation experiments determined CD25 (IL-2Rα) and OX40 to be highly upregulated activation-induced markers (AIM) on the surface of GC Tfh cells after stimulation. In comparison with intracellular cytokine staining, the AIM assay identified >10-fold more Ag-specific GC Tfh cells in HIV Env protein-immunized macaques (BG505 SOSIP). CD4 T cells in blood were also studied. In summary, AIM demonstrates that Ag-specific GC Tfh cells are intrinsically stingy producers of cytokines, which is likely an essential part of their biological function.

摘要

相似文献

[1]
Cytokine-Independent Detection of Antigen-Specific Germinal Center T Follicular Helper Cells in Immunized Nonhuman Primates Using a Live Cell Activation-Induced Marker Technique.

J Immunol. 2016-8-1

[2]
A Cytokine-Independent Approach To Identify Antigen-Specific Human Germinal Center T Follicular Helper Cells and Rare Antigen-Specific CD4+ T Cells in Blood.

J Immunol. 2016-8-1

[3]
Vaccine Induction of Lymph Node-Resident Simian Immunodeficiency Virus Env-Specific T Follicular Helper Cells in Rhesus Macaques.

J Immunol. 2016-2-15

[4]
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[5]
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[6]
Cytokine Expression by T Follicular Helper Cells.

Methods Mol Biol. 2017

[7]
Circulating CXCR5+CD4+helper T cells in systemic lupus erythematosus patients share phenotypic properties with germinal center follicular helper T cells and promote antibody production.

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[8]
Germinal Center T Follicular Helper Cells Are Highly Permissive to HIV-1 and Alter Their Phenotype during Virus Replication.

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[9]
Induction of Th1-Biased T Follicular Helper (Tfh) Cells in Lymphoid Tissues during Chronic Simian Immunodeficiency Virus Infection Defines Functionally Distinct Germinal Center Tfh Cells.

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[10]
OX40 Cooperates with ICOS To Amplify Follicular Th Cell Development and Germinal Center Reactions during Infection.

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[8]
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[9]
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[10]
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本文引用的文献

[1]
A Cytokine-Independent Approach To Identify Antigen-Specific Human Germinal Center T Follicular Helper Cells and Rare Antigen-Specific CD4+ T Cells in Blood.

J Immunol. 2016-8-1

[2]
CXCL13 is a plasma biomarker of germinal center activity.

Proc Natl Acad Sci U S A. 2016-3-8

[3]
HIV and Tfh Cells: Circulating New Ideas to Identify and Protect.

Immunity. 2016-1-19

[4]
Vaccine Induction of Lymph Node-Resident Simian Immunodeficiency Virus Env-Specific T Follicular Helper Cells in Rhesus Macaques.

J Immunol. 2016-2-15

[5]
Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-neutralizing Epitopes.

Cell. 2015-12-17

[6]
Reversible Reprogramming of Circulating Memory T Follicular Helper Cell Function during Chronic HIV Infection.

J Immunol. 2015-12-15

[7]
Germinal center selection and the antibody response to influenza.

Cell. 2015-10-22

[8]
Follicular regulatory T cells impair follicular T helper cells in HIV and SIV infection.

Nat Commun. 2015-10-20

[9]
Decreased T Follicular Regulatory Cell/T Follicular Helper Cell (TFH) in Simian Immunodeficiency Virus-Infected Rhesus Macaques May Contribute to Accumulation of TFH in Chronic Infection.

J Immunol. 2015-10-1

[10]
Quality and quantity of TFH cells are critical for broad antibody development in SHIVAD8 infection.

Sci Transl Med. 2015-7-29

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