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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

Contact between HIV-MDM and PBL is required to induce apoptosis of T lymphocytes. Macrophages that were either HIV- or mock- infected were coincubated with PBL from HIV seropositive individuals with either the two cell populations in direct contact (−), or with contact interrupted (+) by a semipermeable transwell. The mean spontaneous apoptosis in these experiments was 11.0 ± 3.4%.
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Figure 3: Contact between HIV-MDM and PBL is required to induce apoptosis of T lymphocytes. Macrophages that were either HIV- or mock- infected were coincubated with PBL from HIV seropositive individuals with either the two cell populations in direct contact (−), or with contact interrupted (+) by a semipermeable transwell. The mean spontaneous apoptosis in these experiments was 11.0 ± 3.4%.

Mentions: Human macrophages express apoptosis-inducing ligands such as FasL and TNF (40, 42). Because these two apoptosis-inducing ligands may participate in CD4+ T cell apoptosis and are known to be expressed in both cell-associated and soluble form (21), we investigated whether direct cell contact between MDM and PBL is required for CD4+ T cell apoptosis. HIV- or mock-infected MDM were coincubated with PBL from another series of five HIV-infected individuals, in the presence or absence of transwells. Apoptosis of CD4+ T cells was then analyzed by flow cytometry. CD4+ T cell apoptosis mediated by mock-infected MDM (NI) was decreased in the presence of transwells in all patients tested (Fig. 3, compare lanes 1 and 2). Similarly, the higher level of CD4+ T cell apoptosis mediated by HIV-infected MDM (HIV) was also decreased in the presence of transwells (Fig. 3, compare lanes 3 and 4). These results support the requirement for direct contact between MDM and PBL to result in the selective apoptosis of CD4+ T cells from HIVinfected individuals.


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)

Contact between HIV-MDM and PBL is required to induce apoptosis of T lymphocytes. Macrophages that were either HIV- or mock- infected were coincubated with PBL from HIV seropositive individuals with either the two cell populations in direct contact (−), or with contact interrupted (+) by a semipermeable transwell. The mean spontaneous apoptosis in these experiments was 11.0 ± 3.4%.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Contact between HIV-MDM and PBL is required to induce apoptosis of T lymphocytes. Macrophages that were either HIV- or mock- infected were coincubated with PBL from HIV seropositive individuals with either the two cell populations in direct contact (−), or with contact interrupted (+) by a semipermeable transwell. The mean spontaneous apoptosis in these experiments was 11.0 ± 3.4%.
Mentions: Human macrophages express apoptosis-inducing ligands such as FasL and TNF (40, 42). Because these two apoptosis-inducing ligands may participate in CD4+ T cell apoptosis and are known to be expressed in both cell-associated and soluble form (21), we investigated whether direct cell contact between MDM and PBL is required for CD4+ T cell apoptosis. HIV- or mock-infected MDM were coincubated with PBL from another series of five HIV-infected individuals, in the presence or absence of transwells. Apoptosis of CD4+ T cells was then analyzed by flow cytometry. CD4+ T cell apoptosis mediated by mock-infected MDM (NI) was decreased in the presence of transwells in all patients tested (Fig. 3, compare lanes 1 and 2). Similarly, the higher level of CD4+ T cell apoptosis mediated by HIV-infected MDM (HIV) was also decreased in the presence of transwells (Fig. 3, compare lanes 3 and 4). These results support the requirement for direct contact between MDM and PBL to result in the selective apoptosis of CD4+ T cells from HIVinfected individuals.

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