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, Savita G Pahwa

Research output: Contribution to journalArticle

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Abstract

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-2(d/m) population expressed high levels of Fas antigen. Bax, an antagonist of Bcl-2, was brightly expressed even in the Bcl-2(d00d/m) 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.

Original languageEnglish
Pages (from-to)745-753
Number of pages9
JournalBlood
Volume90
Issue number2
StatePublished - Jul 15 1997
Externally publishedYes

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T-cells
Lymphocytes
Virus Diseases
Viruses
Interleukin-2
Modulation
HIV
Apoptosis
T-Lymphocytes
Human Immunodeficiency Virus env Gene Products
Proteins
CD95 Antigens
Fas Ligand Protein
Proto-Oncogenes
Population
Ligation
HIV-1
Monoclonal Antibodies

ASJC Scopus subject areas

  • Hematology

Cite this

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. / Hashimoto, Futoshi; Oyaizu, Naoki; Kalyanaraman, Vaniambadi S.; Pahwa, Savita G.

In: Blood, Vol. 90, No. 2, 15.07.1997, p. 745-753.

Research output: Contribution to journalArticle

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