1. High Levels of Human Immunodeficiency Virus Infection of CD8 Lymphocytes Expressing CD4 In Vivo
- Author
-
Gordon Scott, Peter Simmonds, Stuart Imlach, Clifford Leen, Alexandra Cochrane, and Dermot Kennedy
- Subjects
Adult ,CD4-Positive T-Lymphocytes ,Lymphocyte ,Immunology ,HIV Infections ,CD8-Positive T-Lymphocytes ,Microbiology ,Models, Biological ,Virus ,Antigens, CD4 ,Acquired immunodeficiency syndrome (AIDS) ,In vivo ,T-Lymphocyte Subsets ,Virology ,medicine ,Humans ,HIV Long Terminal Repeat ,biology ,Base Sequence ,HIV ,Cell Differentiation ,Middle Aged ,biology.organism_classification ,medicine.disease ,medicine.anatomical_structure ,Phenotype ,Insect Science ,Lentivirus ,CD4 Antigens ,DNA, Viral ,Pathogenesis and Immunity ,Viral disease ,CD8 - Abstract
Human immunodeficiency virus (HIV)-infected CD8 lymphocytes have been reported in vivo, but the mechanism of infection remains unclear. Experiments using the thy/hu mouse model support export of intrathymically infected CD8 precursors, while recent in vitro data suggest that mature CD8 lymphocytes upregulate CD4 upon activation (generating a CD8brightCD4dimphenotype) and are susceptible to HIV infection. To determine whether these mechanisms operate in vivo and to assess their relative importance in the generation of circulating HIV-infected CD8 lymphocytes, we quantified HIV long terminal repeat (LTR) DNA in CD8+CD4−and CD8brightCD4dimlymphocytes isolated from HIV-infected individuals by fluorescence-activated cell sorting. HIV infection of CD8 lymphocytes was demonstrated in 17 of 19 subjects, with a significant inverse relationship between level of infection and CD4 lymphocyte count (R= −0.73;P< 0.001). The level of HIV infection of CD8brightCD4dimlymphocytes was significantly higher (median, 1,730 HIV LTR copies/106cells;n= 9) than that of CD8+CD4−lymphocytes (undetectable in seven of nine individuals;P< 0.01) and approached that of CD4 lymphocytes from the same individuals (median, 3,660 HIV LTR copies/106cells). CD8brightCD4dimlymphocytes represented 0.8 to 3.3% of total CD8 lymphocytes and were most prevalent in the memory subset. Thus, HIV-infected CD8 lymphocytes commonly circulate in HIV-infected individuals and are generated through infection of activated CD8 lymphocytes rather than through export of intrathymically infected precursors. The high level of infection of CD8brightCD4dimlymphocytes could have a direct role in the decline in CD8 lymphocyte function that accompanies HIV disease progression.
- Published
- 2004