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Macrophage-dependent apoptosis of CD4+ T lymphocytes from HIV-infected individuals is mediated by FasL and tumor necrosis factor.

Badley AD, Dockrell D, Simpson M, Schut R, Lynch DH, Leibson P, Paya CV - J. Exp. Med. (1997)

Bottom Line: This study addresses whether antigen-presenting cells such as human macrophages mediate apoptosis of CD4+ T cells from HIV-infected individuals.Uninfected human macrophages, and to a larger degree, HIV-infected macrophages mediate apoptosis of T cells from HIV-infected, but not from uninfected control individuals.These results support a role for macrophage-associated FasL and TNF in the selective depletion of CD4+ T cells in HIV-infected individuals.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota 55901, USA.

ABSTRACT
Apoptosis of bystander uninfected CD4+ T lymphocytes by neighboring HIV-infected cells is observed in cell culture and in lymphoid tissue of HIV-infected individuals. This study addresses whether antigen-presenting cells such as human macrophages mediate apoptosis of CD4+ T cells from HIV-infected individuals. Uninfected human macrophages, and to a larger degree, HIV-infected macrophages mediate apoptosis of T cells from HIV-infected, but not from uninfected control individuals. This macrophage-dependent killing targets CD4+, but not CD8+ T lymphocytes from HIV-infected individuals, and direct contact between macrophages and lymphocytes is required. Additional analyses indicated that the apoptosis-inducing ligands, FasL and tumor necrosis factor (TNF), mediate this macrophage-induced apoptosis of CD4+ T cells. These results support a role for macrophage-associated FasL and TNF in the selective depletion of CD4+ T cells in HIV-infected individuals.

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Related in: MedlinePlus

HIV-infected macrophages induce selective apoptosis of CD4+ T cells from HIV-infected individuals. 106 PBL from HIV-infected and HIV  seronegative healthy individuals were coincubated with varying amounts (0, 1, 2, 5, and 10 × 106/well) of HIV-infected macrophages for 36 h, and  stained with anti-CD3 FITC, anti-CD4+ PE, and Hoechst 33342. The observed amounts of apoptosis for CD4 lymphocytes (CD3+, CD4+) and CD8  lymphocytes (CD3+, CD4−) are shown. Spontaneous apoptosis is defined as the degree of apoptosis of PBL incubated in the absence of MDM.
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Figure 2: HIV-infected macrophages induce selective apoptosis of CD4+ T cells from HIV-infected individuals. 106 PBL from HIV-infected and HIV seronegative healthy individuals were coincubated with varying amounts (0, 1, 2, 5, and 10 × 106/well) of HIV-infected macrophages for 36 h, and stained with anti-CD3 FITC, anti-CD4+ PE, and Hoechst 33342. The observed amounts of apoptosis for CD4 lymphocytes (CD3+, CD4+) and CD8 lymphocytes (CD3+, CD4−) are shown. Spontaneous apoptosis is defined as the degree of apoptosis of PBL incubated in the absence of MDM.

Mentions: Because CD4+ T lymphocytes are preferentially depleted over CD4+ T cells in HIV-infected individuals, we sought to determine whether MDM induced apoptosis of T lymphocytes is restricted to CD4+ T cells. For this, PBL from five different HIV seropositive individuals (HIV-PBL) were incubated with HIV-infected MDM (HIV-MDM) at different effector (HIV-MDM) to target (HIV-PBL) ratios. After 36 h of coincubation, PBLs were analyzed using flow cytometry to determine the level of apoptosis with CD4+ and CD8+ T cells. Spontaneous apoptosis was higher in CD8+ than CD4+ T cells (Fig. 2). Increasing the effector to target ratio resulted in a progressive increase in the level of CD4+ T cell apoptosis in all patients, an effect that was not observed in CD8+ T lymphocytes from the same HIVinfected individual (Fig. 2). These results indicate that MDM can trigger selective apoptosis of susceptible CD4+ T lymphocytes.


Macrophage-dependent apoptosis of CD4+ T lymphocytes from HIV-infected individuals is mediated by FasL and tumor necrosis factor.

Badley AD, Dockrell D, Simpson M, Schut R, Lynch DH, Leibson P, Paya CV - J. Exp. Med. (1997)

HIV-infected macrophages induce selective apoptosis of CD4+ T cells from HIV-infected individuals. 106 PBL from HIV-infected and HIV  seronegative healthy individuals were coincubated with varying amounts (0, 1, 2, 5, and 10 × 106/well) of HIV-infected macrophages for 36 h, and  stained with anti-CD3 FITC, anti-CD4+ PE, and Hoechst 33342. The observed amounts of apoptosis for CD4 lymphocytes (CD3+, CD4+) and CD8  lymphocytes (CD3+, CD4−) are shown. Spontaneous apoptosis is defined as the degree of apoptosis of PBL incubated in the absence of MDM.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196110&req=5

Figure 2: HIV-infected macrophages induce selective apoptosis of CD4+ T cells from HIV-infected individuals. 106 PBL from HIV-infected and HIV seronegative healthy individuals were coincubated with varying amounts (0, 1, 2, 5, and 10 × 106/well) of HIV-infected macrophages for 36 h, and stained with anti-CD3 FITC, anti-CD4+ PE, and Hoechst 33342. The observed amounts of apoptosis for CD4 lymphocytes (CD3+, CD4+) and CD8 lymphocytes (CD3+, CD4−) are shown. Spontaneous apoptosis is defined as the degree of apoptosis of PBL incubated in the absence of MDM.
Mentions: Because CD4+ T lymphocytes are preferentially depleted over CD4+ T cells in HIV-infected individuals, we sought to determine whether MDM induced apoptosis of T lymphocytes is restricted to CD4+ T cells. For this, PBL from five different HIV seropositive individuals (HIV-PBL) were incubated with HIV-infected MDM (HIV-MDM) at different effector (HIV-MDM) to target (HIV-PBL) ratios. After 36 h of coincubation, PBLs were analyzed using flow cytometry to determine the level of apoptosis with CD4+ and CD8+ T cells. Spontaneous apoptosis was higher in CD8+ than CD4+ T cells (Fig. 2). Increasing the effector to target ratio resulted in a progressive increase in the level of CD4+ T cell apoptosis in all patients, an effect that was not observed in CD8+ T lymphocytes from the same HIVinfected individual (Fig. 2). These results indicate that MDM can trigger selective apoptosis of susceptible CD4+ T lymphocytes.

Bottom Line: This study addresses whether antigen-presenting cells such as human macrophages mediate apoptosis of CD4+ T cells from HIV-infected individuals.Uninfected human macrophages, and to a larger degree, HIV-infected macrophages mediate apoptosis of T cells from HIV-infected, but not from uninfected control individuals.These results support a role for macrophage-associated FasL and TNF in the selective depletion of CD4+ T cells in HIV-infected individuals.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota 55901, USA.

ABSTRACT
Apoptosis of bystander uninfected CD4+ T lymphocytes by neighboring HIV-infected cells is observed in cell culture and in lymphoid tissue of HIV-infected individuals. This study addresses whether antigen-presenting cells such as human macrophages mediate apoptosis of CD4+ T cells from HIV-infected individuals. Uninfected human macrophages, and to a larger degree, HIV-infected macrophages mediate apoptosis of T cells from HIV-infected, but not from uninfected control individuals. This macrophage-dependent killing targets CD4+, but not CD8+ T lymphocytes from HIV-infected individuals, and direct contact between macrophages and lymphocytes is required. Additional analyses indicated that the apoptosis-inducing ligands, FasL and tumor necrosis factor (TNF), mediate this macrophage-induced apoptosis of CD4+ T cells. These results support a role for macrophage-associated FasL and TNF in the selective depletion of CD4+ T cells in HIV-infected individuals.

Show MeSH
Related in: MedlinePlus