title: Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production.
abstract: In the present study, we have investigated the distribution of HIV-specific and HIV-infected CD4 T cells within different populations of memory CD4 T cells isolated from lymph nodes of viremic HIV-infected subjects. Four memory CD4 T cell populations were identified on the basis of the expression of CXCR5, PD-1, and Bcl-6: CXCR5(-)PD-1(-)Bcl-6(-), CXCR5(+)PD-1(-)Bcl-6(-), CXCR5(-)PD-1(+)Bcl-6(-), and CXCR5(+)PD-1(+)Bcl-6(+). On the basis of Bcl-6 expression and functional properties (IL-21 production and B cell help), the CXCR5(+)PD-1(+)Bcl-6(+) cell population was considered to correspond to the T follicular helper (Tfh) cell population. We show that Tfh and CXCR5(-)PD-1(+) cell populations are enriched in HIV-specific CD4 T cells, and these populations are significantly increased in viremic HIV-infected subjects as compared with healthy subjects. The Tfh cell population contained the highest percentage of CD4 T cells harboring HIV DNA and was the most efficient in supporting productive infection in vitro. Replication competent HIV was also readily isolated from Tfh cells in subjects with nonprogressive infection and low viremia (<1,000 HIV RNA copies). However, only the percentage of Tfh cells correlated with the levels of plasma viremia. These results demonstrate that Tfh cells serve as the major CD4 T cell compartment for HIV infection, replication, and production.
authors.affiliation: Divisions of Immunology and Allergy, Lausanne University Hospital, University of Lausanne, CH-1011 Lausanne, Switzerland.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Perreau
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Savoye
authors.forename: Elisa
authors.initials: E
authors.lastname: De Crignis
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Corpataux
authors.forename: Rafael
authors.initials: R
authors.lastname: Cubas
authors.forename: Elias K
authors.initials: EK
authors.lastname: Haddad
authors.forename: Laurence
authors.initials: L
authors.lastname: De Leval
authors.forename: Cecilia
authors.initials: C
authors.lastname: Graziosi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D004268:DNA-Binding Proteins / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory; D007378:Interleukins / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000821:virology; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D054380:Receptors, CXCR5 / Q000378:metabolism; D012016:Reference Values; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000821:virology*; D014766:Viremia / Q000276:immunology; D014779:Virus Replication; D000098546:Interleukin-21
chemical_list: C084103:BCL6 protein, human; C095085:CXCR5 protein, human; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D007378:Interleukins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D051560:Proto-Oncogene Proteins c-bcl-6; D054380:Receptors, CXCR5; D000098546:Interleukin-21