title: Naive and Memory CD4⁺ T Cells Are Differentially Affected in Indonesian HIV Patients Responding to ART.
abstract: While most HIV patients beginning antiretroviral therapy (ART) with advanced immunodeficiency recover CD4(+) T cell numbers, the profiles and functions of the newly acquired CD4(+) T cells have not been monitored in a resource-limiting setting. In this study, HIV patients (n = 31) from Jakarta, Indonesia, were studied 9 months after commencing ART with nadir CD4(+) T cell counts <200 cells/μL. All patients were hepatitis C virus (HCV) seropositive, but asymptomatic. Twelve healthy age-matched controls from the same community were included. CD4(+) T cell subsets, immune activation (HLA-DR), and expression of the interleukin (IL)-7 receptor α chain (CD127) were quantitated by flow cytometry. Proliferation (expression of Ki67) was measured following in vitro stimulation (5 days) with anti-CD3 antibody or IL-7. Fifty-two percent of patients recovered CD4(+) T cell counts >200 cells/μL over 12 months. At 9 months, patients had fewer naive and CD31(+)-naive CD4(+) T cells, more effector memory (EM) CD4(+) T cells, and higher HLA-DR expression on CD4(+) T cells than controls. CD127 expression was low on all CD4(+) T cell subsets except for naive cells, where it was similar to controls. Similarly, after anti-CD3 antibody or IL-7 stimulation, patients had lower Ki67 expression than controls in all subsets, except naive CD4(+) T cells where it was normal or elevated. Overall in the first year of ART, patients had fewer naive and more EM CD4(+) T cells. Ongoing immune activation and, antigen-driven stimulation and differentiation of naive T cells may reduce the naive T cell pool, while driving the maturation and accumulation of memory cells with proliferative defects.
authors.affiliation: 1 School of Pathology and Laboratory Medicine, University of Western Australia , Perth, Australia .
authors.forename: Sara
authors.initials: S
authors.lastname: Tanaskovic
authors.affiliation: 1 School of Pathology and Laboratory Medicine, University of Western Australia , Perth, Australia .
authors.forename: Sonia
authors.initials: S
authors.lastname: Fernandez
authors.affiliation: 2 Virology and Cancer Pathobiology Research Centre for Health Service, University of Indonesia , Jakarta, Indonesia .
authors.forename: Henny
authors.initials: H
authors.lastname: Saraswati
authors.affiliation: 3 School of Medicine, University of Indonesia/Cipto Mangunkusumo Hospital , Jakarta, Indonesia .
authors.forename: Evy
authors.initials: E
authors.lastname: Yunihastuti
authors.affiliation: 3 School of Medicine, University of Indonesia/Cipto Mangunkusumo Hospital , Jakarta, Indonesia .
authors.forename: Rino A
authors.initials: RA
authors.lastname: Gani
authors.affiliation: 3 School of Medicine, University of Indonesia/Cipto Mangunkusumo Hospital , Jakarta, Indonesia .
authors.forename: Samsuridjal
authors.initials: S
authors.lastname: Djauzi
authors.affiliation: 3 School of Medicine, University of Indonesia/Cipto Mangunkusumo Hospital , Jakarta, Indonesia .|4 School of Biomedical Science, Curtin University of Technology , Perth, Australia .
authors.forename: Patricia
authors.initials: P
authors.lastname: Price
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D006508:Hepatitis Antibodies / Q000097:blood; D006801:Humans; D016130:Immunophenotyping; D007214:Indonesia; D015851:Interleukin-7 / Q000494:pharmacology; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism*; D008297:Male; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D006684:HLA-DR Antigens; D006508:Hepatitis Antibodies; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D011948:Receptors, Antigen, T-Cell