title: Distinct kinetics of Gag-specific CD4+ and CD8+ T cell responses during acute HIV-1 infection.
abstract: HIV infection is characterized by a gradual deterioration of immune function, mainly in the CD4 compartment. To better understand the dynamics of HIV-specific T cells, we analyzed the kinetics and polyfunctional profiles of Gag-specific CD4(+) and CD8(+) T cell responses in 12 subtype C-infected individuals with different disease-progression profiles, ranging from acute to chronic HIV infection. The frequencies of Gag-responsive CD4(+) and CD8(+) T cells showed distinct temporal kinetics. The peak frequency of Gag-responsive IFN-γ(+)CD4(+) T cells was observed at a median of 28 d (interquartile range: 21-81 d) post-Fiebig I/II staging, whereas Gag-specific IFN-γ(+)CD8(+) T cell responses peaked at a median of 253 d (interquartile range: 136-401 d) and showed a significant biphasic expansion. The proportion of TNF-α-expressing cells within the IFN-γ(+)CD4(+) T cell population increased (p = 0.001) over time, whereas TNF-α-expressing cells within IFN-γ(+)CD8(+) T cells declined (p = 0.005). Both Gag-responsive CD4(+) and CD8(+) T cells showed decreased Ki67 expression within the first 120 d post-Fiebig I/II staging. Prior to the disappearance of Gag-responsive Ki67(+)CD4(+) T cells, these cells positively correlated (p = 0.00038) with viremia, indicating that early Gag-responsive CD4 events are shaped by viral burden. No such associations were observed in the Gag-specific CD8(+) T cell compartment. Overall, these observations indicated that circulating Gag-responsive CD4(+) and CD8(+) T cell frequencies and functions are not synchronous, and properties change rapidly at different tempos during early HIV infection.
authors.affiliation: Division of Immunology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town 7529, South Africa.
authors.forename: Catherine
authors.initials: C
authors.lastname: Riou
authors.forename: Vitaly V
authors.initials: VV
authors.lastname: Ganusov
authors.forename: Suzanne
authors.initials: S
authors.lastname: Campion
authors.forename: Mandla
authors.initials: M
authors.lastname: Mlotshwa
authors.forename: Michael K P
authors.initials: MK
authors.lastname: Liu
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Whale
authors.forename: Nilu
authors.initials: N
authors.lastname: Goonetilleke
authors.forename: Persephone
authors.initials: P
authors.lastname: Borrow
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.forename: Michael R
authors.initials: MR
authors.lastname: Betts
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: Clive M
authors.initials: CM
authors.lastname: Gray
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D002478:Cells, Cultured; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D013997:Time Factors; D055815:Young Adult; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D054301:gag Gene Products, Human Immunodeficiency Virus