Variations in CD4 expression by human monocytes and macrophages and their relationships to infection with the human immunodeficiency virus.
The expression of CD4 antigen on the surface of LeuM3-positive human blood monocytes was found to be variable with 65 to 90% of cells from 46 normal human volunteers being positive by dual staining flow cytometry. When monocytes adhered to plastic (but not when cultured on Teflon), a marked decrease in CD4 expression was observed between 1 and 24 h post-adherence. CD4 expression could not be detected in macrophages adhered to plastic for 5 days by using four anti-CD4 monoclonal antibodies in flow cytometry or direct immunofluorescence. Conversely an increasing proportion of adherent cells expressed LeuM3 and OKM5 surface antigens over the 5 days. CD4 mRNA levels were measured by slot-blot and Northern hybridization, and total cellular CD4 protein levels by immunoprecipitation. Both cellular mRNA and CD4 levels remained constant throughout the 5 day period but membrane CD4 protein levels were greatly reduced indicating that the down-regulation of CD4 was post-translational. Infection with two of six fresh human immunodeficiency virus (HIV) isolates showed different kinetic patterns when tested on purified monocytes recently adhered to plastic and macrophages adherent for 5 days. HIV antigen and reverse transcriptase levels in infected monocyte cultures remained high for 3 to 4 weeks before detachment and necrosis of the cells occurred. Infection of macrophages generated much lower levels of antigen and reverse transcriptase which declined to very low or undetectable levels over 2 weeks, leaving persisting viable macrophages. One week after infection HIV nucleic acid was detected in 69 +/- 7% of monocytes and 6 +/- 3% of macrophages by in situ hybridization. Blocking experiments with anti-Leu3a monoclonal antibody suggested that HIV infection of 5 day adherent macrophages occurred mainly by a mechanism other than binding to CD4.
Kazazi
F
F
Virology, Unit Westmead Hospital, New South Wales, Australia.
Mathijs
J M
JM
Foley
P
P
Cunningham
A L
AL
D015704:CD4 Antigens / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion; D015342:DNA Probes; D004279:DNA, Viral / Q000032:analysis; D005786:Gene Expression Regulation; D006678:HIV / Q000254:growth & development*; D006801:Humans; D007158:Immunologic Techniques; D008264:Macrophages / Q000382:microbiology* / Q000502:physiology; D008970:Molecular Weight; D009000:Monocytes / Q000382:microbiology / Q000502:physiology; D009693:Nucleic Acid Hybridization; D010969:Plastics; D011138:Polytetrafluoroethylene
D015704:CD4 Antigens; D015342:DNA Probes; D004279:DNA, Viral; D010969:Plastics; D011138:Polytetrafluoroethylene