Activation of CD8+ T lymphocytes through the T cell receptor turns on CD4 gene expression: implications for HIV pathogenesis.
T cell activation through the T cell receptor is necessary to achieve a specific and effective immune response. We report here that stimulation of CD8+ T cells through the T cell receptor complex leads to de novo expression of the CD4 antigen on the cell surface that results in susceptibility of CD8+ T cells to HIV infection. In addition, activation of peripheral blood mononuclear cells from HIV-infected individuals results in the appearance of double-positive CD4+/CD8+ T cells, which become infected by endogenous HIV. HIV DNA sequences could be detected in uncultured and sorted mature CD3+CD8+ T cells from HIV+ individuals. These results suggest a new mechanism by which HIV could attack the immune system and may help to explain the CD8+ T cell defects in AIDS patients.
Flamand
L
L
Institute of Human Virology, University of Maryland Biotechnology Institute at Baltimore, 725 West Lombard Street, Baltimore, MD 21201-1192, USA.
Crowley
R W
RW
Lusso
P
P
Colombini-Hatch
S
S
Margolis
D M
DM
Gallo
R C
RC
D015153:Blotting, Western; D015704:CD4 Antigens / Q000096:biosynthesis* / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000209:etiology*; D015497:HIV-1 / Q000254:growth & development; D006801:Humans; D008213:Lymphocyte Activation; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*
D015704:CD4 Antigens; D004279:DNA, Viral; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell