title: Phenotypic characterization of HIV-specific CD8+ T cells during early and chronic infant HIV-1 infection.
abstract: Although CD8(+) T cells play an important role in the containment of adult HIV-1 replication, their role in infant HIV-1 infection is not as well understood. Impaired HIV-specific CD8(+) T cell responses may underlie the persistently high viral loads observed in infants. We examined the frequency and phenotype of infant HIV-specific CD8(+) T cells in 7 HIV-infected antiretroviral therapy-naïve infants during the first 2 years of life, using class I HLA tetramers and IFN-γ-ELISPOT. The frequency (0.088-3.9% of CD3(+)CD8(+) cells) and phenotype (CD27(+)CD28(-), CD45RA(+/-), CD57(+/-), HLA-DR(+), CD95(+)) of infant HIV-specific CD8(+) T cells were similar to reports in adults undergoing early infection. Unlike adults, at 23-24 months post-infection a high frequency of HIV-specific CD8(+) T cells expressed HLA-DR (mean 80%, range 68-85%) and CD95 (mean 88%, range 79-96%), suggesting sustained activation and vulnerability to apoptosis. Despite comparable expansion of HIV-specific CD8(+) T cells of a similar phenotype to adults during early infection, infant T cells failed to contain HIV-1 replication, and remained persistently activated and vulnerable to apoptosis during chronic infection.
authors.affiliation: MRC Human Immunology Unit, Oxford University, Oxford, United Kingdom. jslyker@uw.edu
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Slyker
authors.forename: Grace C
authors.initials: GC
authors.lastname: John-Stewart
authors.forename: Tao
authors.initials: T
authors.lastname: Dong
authors.forename: Barbara
authors.initials: B
authors.lastname: Lohman-Payne
authors.forename: Marie
authors.initials: M
authors.lastname: Reilly
authors.forename: Ann
authors.initials: A
authors.lastname: Atzberger
authors.forename: Stephen
authors.initials: S
authors.lastname: Taylor
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Maleche-Obimbo
authors.forename: Dorothy
authors.initials: D
authors.lastname: Mbori-Ngacha
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Rowland-Jones
mesh_terms: D018106:CD28 Antigens / Q000378:metabolism; D018959:CD57 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017493:Leukocyte Common Antigens / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: D018106:CD28 Antigens; D018959:CD57 Antigens; D006684:HLA-DR Antigens; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D019014:fas Receptor; D017493:Leukocyte Common Antigens