High levels of human immunodeficiency virus infection of CD8 lymphocytes expressing CD4 in vivo.
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 CD8bright CD4dim phenotype) 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 CD8bright CD4dim lymphocytes 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 CD8bright CD4dim lymphocytes was significantly higher (median, 1,730 HIV LTR copies/10(6) cells; 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/10(6) cells). CD8bright CD4dim lymphocytes 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 CD8bright CD4dim lymphocytes could have a direct role in the decline in CD8 lymphocyte function that accompanies HIV disease progression.
Laboratory for Clinical and Molecular Virology, University of Edinburgh, Edinburgh EH9 1QH, United Kingdom. alex.cochrane@ed.ac.uk
Alexandra
A
Cochrane
Stuart
S
Imlach
Clifford
C
Leen
Gordon
G
Scott
Dermot
D
Kennedy
Peter
P
Simmonds
D000328:Adult; D001483:Base Sequence; D015704:CD4 Antigens / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D002454:Cell Differentiation; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D006678:HIV / Q000235:genetics / Q000302:isolation & purification*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D016325:HIV Long Terminal Repeat; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology / Q000821:virology
D015704:CD4 Antigens; D004279:DNA, Viral