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Modulation of Bcl-2 Protein by CD4 Cross-Linking: A Possible Mechanism for Lymphocyte Apoptosis in Human Immunodeficiency Virus Infection and for Rescue of Apoptosis by Interleukin-2
Futoshi Hashimoto,
Naoki Oyaizu,
Vaniambadi S. Kalyanaraman, and
Savita Pahwa
From the Department of Pediatrics, North Shore University Hospital-New York University School of Medicine, Manhasset, NY and Advanced BioScience Laboratories, Inc, Kensington, MD.
We have previously demonstrated that CD4 cross-linking (CD4XL) results in apoptosis of CD4+ T cells and augmentation of Fas antigen (CD95, APO-1) expression in CD4+ and CD8+ T cells. Here we demonstrate that CD4XL mediated by both, anti-CD4 monoclonal antibody (MoAb) or human immunodeficiency virus (HIV) envelope protein gp120 reduces the expression of the proto-oncogene Bcl-2 in CD4+ T cells, but not in CD8+ T cells, concurrently with the induction of CD4+ T cell-apoptosis. Additionally, the Bcl-2dim population expressed high levels of Fas antigen. Bax, an antagonist of Bcl-2, was brightly expressed even in the Bcl-2dim population. Addition of interleukin (IL)-2 rescued CD4+ T cells from CD4XL-induced Bcl-2 downmodulation and apoptosis induction. These results support the hypothesis that CD4 ligation by HIV-1 envelope protein in vivo in HIV-infected patients selectively reduces Bcl-2 protein in CD4+ T lymphocytes, thereby facilitating Fas/Fas-ligand triggered apoptosis; furthermore the findings reported expand the rationale for use of IL-2 in HIV disease.
Blood, Vol. 90 No. 2 (July 15), 1997:
pp. 745-753
© 1997 by The American Society of Hematology.
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