title: Regulatory and Helper Follicular T Cells and Antibody Avidity to Simian Immunodeficiency Virus Glycoprotein 120.
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.
authors: Animal Models and Retroviral Vaccine Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors: Matthew J
authors: MJ
authors: Blackburn
authors: California National Primate Research Center, University of California Davis, Davis, CA 95616;
authors: Ma
authors: M
authors: Zhong-Min
authors: Animal Models and Retroviral Vaccine Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors: Francesca
authors: F
authors: Caccuri
authors: Animal Models and Retroviral Vaccine Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors: Katherine
authors: K
authors: McKinnon
authors: Animal Models and Retroviral Vaccine Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors: Luca
authors: L
authors: Schifanella
authors: Department of Microbial Pathogenesis, University of Maryland School of Dentistry, Baltimore, MD 21201; and.
authors: Yongjun
authors: Y
authors: Guan
authors: Animal Models and Retroviral Vaccine Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors: Giacomo
authors: G
authors: Gorini
authors: Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20852.
authors: David
authors: D
authors: Venzon
authors: Animal Models and Retroviral Vaccine Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors: Claudio
authors: C
authors: Fenizia
authors: Animal Models and Retroviral Vaccine Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors: Nicolò
authors: N
authors: Binello
authors: Animal Models and Retroviral Vaccine Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors: Shari N
authors: SN
authors: Gordon
authors: California National Primate Research Center, University of California Davis, Davis, CA 95616;
authors: Christopher J
authors: CJ
authors: Miller
authors: Animal Models and Retroviral Vaccine Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
authors: Genoveffa
authors: G
authors: Franchini
authors: Animal Models and Retroviral Vaccine Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; vaccarim@mail.nih.gov.
authors: Monica
authors: M
authors: Vaccari
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000915:Antibody Affinity / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology; D017252:CD3 Complex / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D002465:Cell Movement; D049109:Cell Proliferation; D051858:Forkhead Transcription Factors / Q000378:metabolism; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D008253:Macaca mulatta; D008562:Membrane Glycoproteins / Q000276:immunology*; D054400:Receptors, CCR7 / Q000235:genetics; D054380:Receptors, CXCR5 / Q000096:biosynthesis / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D017252:CD3 Complex; D051858:Forkhead Transcription Factors; D008562:Membrane Glycoproteins; D054400:Receptors, CCR7; D054380:Receptors, CXCR5; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus