title: Discordance between frequency of human immunodeficiency virus type 1 (HIV-1)-specific gamma interferon-producing CD4(+) T cells and HIV-1-specific lymphoproliferation in HIV-1-infected subjects with active viral replication.
abstract: One hallmark of uncontrolled, chronic human immunodeficiency virus type 1 (HIV-1) infection is the absence of strong HIV-1-specific, CD4(+) T-cell-proliferative responses, yet the mechanism underlying this T helper (Th)-cell defect remains controversial. To better understand the impact of HIV-1 replication on Th-cell function, we compared the frequency of CD4(+) Th-cell responses based on production of gamma interferon to lymphoproliferative responses directed against HIV-1 proteins in HIV-1-infected subjects with active in vivo viral replication versus those on suppressed highly active antiretroviral therapy (HAART). No statistically significant differences in the frequencies of cytokine-secreting, HIV-1-specific CD4(+) T cells between the donor groups were found, despite differences in viral load and treatment status. However, HIV-1-specific lymphoproliferative responses were significantly greater in the subjects with HAART suppression than in subjects with active viral replication. Similar levels of HIV-1 RNA were measured in T-cell cultures stimulated with HIV-1 antigens regardless of donor in vivo viral loads, but only HIV-1-specific CD4(+) T cells from subjects with HAART suppression proliferated in vitro, suggesting that HIV-1 replication in vitro does not preclude HIV-1-specific lymphoproliferation. This study demonstrates a discordance between the frequency and proliferative capacity of HIV-1-specific CD4(+) T cells in subjects with ongoing in vivo viral replication and suggests that in vivo HIV-1 replication contributes to the observed defect in HIV-1-specific CD4(+) T-cell proliferation.
authors.affiliation: Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
authors.forename: B E
authors.initials: BE
authors.lastname: Palmer
authors.forename: E
authors.initials: E
authors.lastname: Boritz
authors.forename: N
authors.initials: N
authors.lastname: Blyveis
authors.forename: C C
authors.initials: CC
authors.lastname: Wilson
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology*; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load; D014779:Virus Replication; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016655:HIV Core Protein p24; D007371:Interferon-gamma; D037181:Lectins, C-Type; D012367:RNA, Viral; D000099192:CD69 Antigens