title: A steady state of CD4+ T cell memory maturation and activation is established during primary subtype C HIV-1 infection.
abstract: The functional integrity of CD4(+) T cells is crucial for well-orchestrated immunity and control of HIV-1 infection, but their selective depletion during infection creates a paradox for understanding a protective response. We used multiparameter flow cytometry to measure activation, memory maturation, and multiple functions of total and Ag-specific CD4(+) T cells in 14 HIV-1- and CMV- coinfected individuals at 3 and 12 mo post HIV-1 infection. Primary HIV-1 infection was characterized by elevated levels of CD38, HLA-DR, and Ki67 in total memory and Gag-specific CD4(+) and CD8(+) T cells. In both HIV-infected and 15 uninfected controls, the frequency of activated cells was uniformly distributed among early differentiated (ED; CD45RO(+)CD27(+)), late differentiated (CD45RO(+)CD27(-)), and fully differentiated effector (CD45RO(-)CD27(-)) memory CD4(+) T cells. In HIV-1-infected individuals, activated CD4(+) T cells significantly correlated with viremia at 3 mo postinfection (r = 0.79, p = 0.0007) and also harbored more gag provirus DNA copies than nonactivated cells (p = 0.04). Moreover, Gag-specific ED CD4(+) T cells inversely associated with plasma viral load (r = -0.87, p < 0.0001). Overall, we show that low copy numbers of gag provirus and plasma RNA copies associated with low CD4 activation as well as accumulation of ED HIV-specific CD4(+) memory. Significant positive correlations between 3 and 12 mo activation and memory events highlighted that a steady state of CD4(+) T cell activation and memory maturation was established during primary infection and that these cells were unlikely to be involved in influencing the course of viremia in the first 12 mo of HIV-1 infection.
authors.affiliation: AIDS Research Unit, National Institute for Communicable Diseases, Johannesburg, Gauteng, South Africa.
authors.forename: Pholo
authors.initials: P
authors.lastname: Maenetje
authors.forename: Catherine
authors.initials: C
authors.lastname: Riou
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Casazza
authors.forename: David
authors.initials: D
authors.lastname: Ambrozak
authors.forename: Brenna
authors.initials: B
authors.lastname: Hill
authors.forename: Glenda
authors.initials: G
authors.lastname: Gray
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.forename: Guy
authors.initials: G
authors.lastname: de Bruyn
authors.forename: Clive M
authors.initials: CM
authors.lastname: Gray
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000821:virology; D015331:Cohort Studies; D016384:Consensus Sequence / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D015497:HIV-1 / Q000145:classification* / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000276:immunology*; D011446:Prospective Studies; D019562:Viral Load / Q000276:immunology; D014766:Viremia / Q000276:immunology / Q000473:pathology; D014779:Virus Replication / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D054301:gag Gene Products, Human Immunodeficiency Virus