title: Immunologic profile of highly exposed yet HIV type 1-seronegative men.
abstract: The host immune factors that determine susceptibility to HIV-1 infection are poorly understood. We compared multiple immunologic parameters in three groups of HIV-1-seronegative men: 14 highly exposed (HR10), 7 previously reported possibly to have sustained transient infection (PTI), and a control group of 14 low risk blood bank donors (BB). Virus-specific cellular immune assays were performed for CD4(+) T helper cell responses, CD8(+) cytotoxic T lymphocyte activity, CD8(+) cell chemokine release, and CD8(+) cell-derived antiviral soluble factor activity. General immune parameters evaluated included CCR5 genotype and phenotype, interferon alpha production by PBMCs, leukocyte subset analysis, and detailed T lymphocyte phenotyping. Comparisons revealed no detectable group-specific differences in measures of virus-specific immunity. However, the HR10 group differed from the BB group in several general immune parameters, having higher absolute monocyte counts, higher absolute CD8(+) T cell counts and percentages, lower naive and higher terminal effector CD8(+) cells, and lower levels of CD28(+)CD8(+) cells. These changes were not associated with seropositivity for other chronic viral infections. The PTI men appeared to have normal levels of monocytes and slightly elevated levels of CD8(+) T cells (also with increased effector and decreased naive cells). Although we cannot entirely exclude the contribution of other chronic viral infections, these findings suggest that long-lived systemic cellular antiviral immunity as detected by our assays is not a common mechanism for resistance to infection, and that resistance may be multifactorial. General immune parameters reflected by CD8(+) T cell levels and activation, and monocyte concentrations may affect the risk of infection with HIV-1, and/or serve as markers of exposure.
authors.affiliation: Department of Medicine, UCLA Medical Center, Los Angeles, California 90095, USA.
authors.forename: Otto O
authors.initials: OO
authors.lastname: Yang
authors.forename: W John
authors.initials: WJ
authors.lastname: Boscardin
authors.forename: Jose
authors.initials: J
authors.lastname: Matud
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Hausner
authors.forename: Lance E
authors.initials: LE
authors.lastname: Hultin
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Hultin
authors.forename: Roger
authors.initials: R
authors.lastname: Shih
authors.forename: John
authors.initials: J
authors.lastname: Ferbas
authors.forename: Frederick P
authors.initials: FP
authors.lastname: Siegal
authors.forename: Michael
authors.initials: M
authors.lastname: Shodell
authors.forename: Gene M
authors.initials: GM
authors.lastname: Shearer
authors.forename: Edith
authors.initials: E
authors.lastname: Grene
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: Steve
authors.initials: S
authors.lastname: O'Brien
authors.forename: Charles B
authors.initials: CB
authors.lastname: Price
authors.forename: Roger
authors.initials: R
authors.lastname: Detels
authors.forename: Beth D
authors.initials: BD
authors.lastname: Jamieson
authors.forename: Janis V
authors.initials: JV
authors.lastname: Giorgi
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D019713:Receptors, CCR5 / Q000378:metabolism; D012191:Retroviridae Proteins / Q000737:chemistry; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology
chemical_list: D016207:Cytokines; D010455:Peptides; D019713:Receptors, CCR5; D012191:Retroviridae Proteins; D007371:Interferon-gamma