Apoptosis of CD4+ T cells induced after contact with HIV1-infected or non-infected macrophages.
The hallmark of human immunodeficiency virus type 1 (HIV1) infection is the relentless destruction of CD4+ T lymphocytes. Indirect cell killing mechanisms are thought to play an outstanding role in lymphocyte depletion. One such proposed mechanism is the induction of apoptosis through cross-linking of the CD4 receptor by anti-CD4 antibodies or by the HIV1 envelope protein expressed at the surface of infected cells. Here we provide evidence that apoptosis is triggered in CD4+ lymphoblastoid cells (MT4) following cocultivation with monocyte-derived macrophages (MDMs) productively infected with the monocytotropic isolate HIV1 PAR. Blocking virus replication by AZT abrogates apoptosis of MT4 cells. Infected MDMs do not transmit virus infection to target cells. DNA nucleosomal fragmentation occurs at 46-66 h after starting cocultures. It is inhibited by the addition of neutralizing anti-gp120 monoclonal antibody (mAb), implying that the gp120/CD4 interaction triggers the apoptotic process. Cocultivating with MDMs, either infected or not, in the presence of anti-CD4 mAb Leu-3a, also leads to MT4 cell death, with DNA fragmentation being detected at 24-40 h. Leu-3a induced apoptosis does not require cross-linking of CD4 by anti-immunoglobulin, showing that MDMs provide an alternative to conventional cross-linking. Both the infected and the non-infected MDMs were found to stimulate 3H-thymidine incorporation in cocultivated MT4 cells.
Godard
C M
CM
INSERM U322, Parc Scientifique et Technologique de Luminy, Marseille, France.
Serriès
H
H
Fulachier
C
C
Chermann
J C
JC
D017209:Apoptosis / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002450:Cell Communication; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology / Q000821:virology*; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000502:physiology; D014779:Virus Replication
D015699:HIV Envelope Protein gp120