Regulatory and Helper Follicular T Cells and Antibody Avidity to Simian Immunodeficiency Virus Glycoprotein 120

Matthew J Blackburn, Ma Zhong-Min, Francesca Caccuri, Katherine McKinnon, Luca Schifanella, Yongjun Guan, Giacomo Gorini, David Venzon, Claudio Fenizia, Nicolò Binello, Shari N Gordon, Christopher J Miller, Genoveffa Franchini, Monica Vaccari

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

T follicular regulatory cells (TFR) are a suppressive CD4(+) T cell subset that migrates to germinal centers (GC) during Ag presentation by upregulating the chemokine receptor CXCR5. In the GC, TFR control T follicular helper cell (TFH) expansion and modulate the development of high-affinity Ag-specific responses. In this study, we identified and characterized TFR as CXCR5(+)CCR7(-) "follicular" T regulatory cells in lymphoid tissues of healthy rhesus macaques, and we studied their dynamics throughout infection in a well-defined animal model of HIV pathogenesis. TFR were infected by SIVmac251 and had comparable levels of SIV DNA to CXCR5(-)CCR7(+) "T zone" T regulatory cells and TFH. Contrary to the SIV-associated TFH expansion in the chronic phase of infection, we observed an apparent reduction of TFR frequency in cell suspension, as well as a decrease of CD3(+)Foxp3(+) cells in the GC of intact lymph nodes. TFR frequency was inversely associated with the percentage of TFH and, interestingly, with the avidity of the Abs that recognize the SIV gp120 envelope protein. Our findings show changes in the TFH/TFR ratio during chronic infection and suggest possible mechanisms for the unchecked expansion of TFH cells in HIV/SIV infection.

Original languageEnglish (US)
Pages (from-to)3227-36
Number of pages10
JournalJournal of immunology (Baltimore, Md. : 1950)
Volume195
Issue number7
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

Bibliographical note

Copyright © 2015 by The American Association of Immunologists, Inc.

Keywords

  • Animals
  • Antibodies, Viral/immunology
  • Antibody Affinity/immunology
  • Antigen Presentation/immunology
  • CD3 Complex/metabolism
  • CD4 Lymphocyte Count
  • Cell Movement
  • Cell Proliferation
  • Forkhead Transcription Factors/metabolism
  • Germinal Center/cytology
  • Macaca mulatta
  • Membrane Glycoproteins/immunology
  • Receptors, CCR7/genetics
  • Receptors, CXCR5/biosynthesis
  • Simian Acquired Immunodeficiency Syndrome/immunology
  • Simian Immunodeficiency Virus/immunology
  • T-Lymphocytes, Helper-Inducer/immunology
  • T-Lymphocytes, Regulatory/immunology
  • Viral Envelope Proteins/immunology

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Intramural

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