title: Selective Loss of Early Differentiated, Highly Functional PD1high CD4 T Cells with HIV Progression.
abstract: The role of PD-1 expression on CD4 T cells during HIV infection is not well understood. Here, we describe the differential expression of PD-1 in CD127high CD4 T cells within the early/intermediate differentiated (EI) (CD27highCD45RAlow) T cell population among uninfected and HIV-infected subjects, with higher expression associated with decreased viral replication (HIV-1 viral load). A significant loss of circulating PD-1highCTLA-4low CD4 T cells was found specifically in the CD127highCD27highCD45RAlow compartment, while initiation of antiretroviral treatment, particularly in subjects with advanced disease, reversed these dynamics. Increased HIV-1 Gag DNA was also found in PD-1high compared to PD-1low ED CD4 T cells. In line with an increased susceptibility to HIV infection, PD-1 expression in this CD4 T cell subset was associated with increased activation and expression of the HIV co-receptor, CCR5. Rather than exhaustion, this population produced more IFN-g, MIP1-a, IL-4, IL-10, and IL-17a compared to PD-1low EI CD4 T cells. In line with our previous findings, PD-1high EI CD4 T cells were also characterized by a high expression of CCR7, CXCR5 and CCR6, a phenotype associated with increased in vitro B cell help. Our data show that expression of PD-1 on early-differentiated CD4 T cells may represent a population that is highly functional, more susceptible to HIV infection and selectively lost in chronic HIV infection.
authors.affiliation: Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.|United States Military HIV Research Program, Silver Spring, Maryland, United States of America.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Paris
authors.affiliation: Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Petrovas
authors.affiliation: Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.
authors.forename: Sara
authors.initials: S
authors.lastname: Ferrando-Martinez
authors.affiliation: Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.|Department of Microbiology and Immunology, University of Miami, Miller School of Medicine, Miami, Florida, United States of America.
authors.forename: Eirini
authors.initials: E
authors.lastname: Moysi
authors.affiliation: Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Boswell
authors.affiliation: Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.
authors.forename: Eva
authors.initials: E
authors.lastname: Archer
authors.affiliation: Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Ambrozak
authors.affiliation: Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Casazza
authors.affiliation: Division of Infectious Diseases, Antiviral Research Center, University of California San Diego, San Diego, California, United States of America.
authors.forename: Richard
authors.initials: R
authors.lastname: Haubrich
authors.affiliation: HIV-Specific Immunity Section, Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Maryland, United States of America.
authors.forename: Mark
authors.initials: M
authors.lastname: Connors
authors.affiliation: United States Military HIV Research Program, Silver Spring, Maryland, United States of America.
authors.forename: Julie
authors.initials: J
authors.lastname: Ake
authors.affiliation: International Vaccine Institute, Seoul, South Korea.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, Maryland, United States of America.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D018450:Disease Progression; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D015497:HIV-1; D006801:Humans; D016133:Polymerase Chain Reaction; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology / Q000502:physiology*; D019713:Receptors, CCR5 / Q000378:metabolism; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; C584933:CCR5 protein, human; D016207:Cytokines; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D019713:Receptors, CCR5