Macrophage-dependent Apoptosis of CD4+ T Lymphocytes from HIV-infected Individuals Is Mediated by FasL and Tumor Necrosis Factor

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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Human herpesvirus 7 induces the functional up-regulation of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) coupled to TRAIL-R1 down-modulation in CD4+ T cells

Blood ◽

10.1182/blood.v98.8.2474 ◽

2001 ◽

Vol 98 (8) ◽

pp. 2474-2481 ◽

Cited By ~ 12

Author(s):

Paola Secchiero ◽

Prisco Mirandola ◽

Davide Zella ◽

Claudio Celeghini ◽

Arianna Gonelli ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Tumor Necrosis Factor ◽

T Lymphocytes ◽

Cd4 T Cells ◽

Tumor Necrosis ◽

Human Herpesvirus ◽

Cell Contact ◽

Cell Infection ◽

Necrosis Factor

Abstract Human herpesvirus 7 (HHV-7) is endemic in the adult human population. Although HHV-7 preferentially infects activated CD4+ T lymphocytes, the consequence of T-cell infection for viral pathogenesis and immunity are still largely unknown. HHV-7 infection induces apoptosis mostly in uninfected bystander cells but not in productively infected CD4+ T cells. To dissect the underlying molecular events, the role of death-inducing ligands belonging to the tumor necrosis factor (TNF) cytokine superfamily was investigated. HHV-7 selectively up-regulated the expression of TNF-related apoptosis-inducing ligand (TRAIL), but not that of CD95 ligand or TNF-α in lymphoblastoid (SupT1) or primary activated CD4+ T cells. Moreover, in a cell-to-cell-contact assay, HHV-7–infected CD4+ T lymphocytes were cytotoxic for bystander uninfected CD4+ T cells through the TRAIL pathway. By contrast, HHV-7 infection caused a marked decrease of surface TRAIL-R1, but not of TRAIL-R2, CD95, TNF-R1, or TNF-R2. Of note, the down-regulation of TRAIL-R1 selectively occurred in cells coexpressing HHV-7 antigens that became resistant to TRAIL-mediated cytotoxicity. These findings suggest that the TRAIL-mediated induction of T-cell death may represent an important immune evasion mechanism of HHV-7, helping the virus to persist in the host organism throughout its lifetime.

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Increased expression of tumor necrosis factor in peripheral blood memory CD4+ T cells of patients with Crohn's disease

Gastroenterology ◽

10.1016/s0016-5085(01)81574-2 ◽

2001 ◽

Vol 120 (5) ◽

pp. A317-A317

Author(s):

J DETENA ◽

L MANZANO ◽

J LEAL ◽

A PRIETO ◽

E ANTONIO ◽

...

Keyword(s):

T Cells ◽

Crohn’S Disease ◽

Tumor Necrosis Factor ◽

Crohn's Disease ◽

Peripheral Blood ◽

Cd4 T Cells ◽

Tumor Necrosis ◽

Memory Cd4 T Cells ◽

Necrosis Factor

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Depletion of tumor necrosis factor receptor superfamily member 9 (TNFRSF9; 4–1BB; CD137)+/CD4 + T cells to improve adoptive cell therapy treatment of cancer

Science-Business eXchange ◽

10.1038/scibx.2012.139 ◽

2012 ◽

Vol 5 (5) ◽

pp. 139-139

Keyword(s):

T Cells ◽

Tumor Necrosis Factor ◽

Cell Therapy ◽

Cd4 T Cells ◽

Tumor Necrosis ◽

Adoptive Cell Therapy ◽

Tumor Necrosis Factor Receptor ◽

Necrosis Factor ◽

Therapy Treatment

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Tumor Necrosis Factor Receptor Expression in HIV-1-Infected CD4+ T Cells

Microbiology and Immunology ◽

10.1111/j.1348-0421.1994.tb02160.x ◽

1994 ◽

Vol 38 (12) ◽

pp. 1005-1008 ◽

Cited By ~ 5

Author(s):

Didier Hober ◽

Donat de Groote ◽

Nathalie Vanpouille ◽

Isabelle Dehart ◽

Lu Shen ◽

...

Keyword(s):

T Cells ◽

Tumor Necrosis Factor ◽

Cd4 T Cells ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Receptor ◽

Receptor Expression ◽

Hiv 1 ◽

Necrosis Factor

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Apolipoprotein A-I inhibits the production of interleukin-1β and tumor necrosis factor-α by blocking contact-mediated activation of monocytes by T lymphocytes

Blood ◽

10.1182/blood.v97.8.2381 ◽

2001 ◽

Vol 97 (8) ◽

pp. 2381-2389 ◽

Cited By ~ 242

Author(s):

Nevila Hyka ◽

Jean-Michel Dayer ◽

Christine Modoux ◽

Tadahiko Kohno ◽

Carl K. Edwards ◽

...

Keyword(s):

T Cells ◽

Tumor Necrosis Factor ◽

T Lymphocytes ◽

Tumor Necrosis ◽

Tumor Necrosis Factor Α ◽

Interleukin 1Β ◽

Apolipoprotein A ◽

Tnf Α ◽

Factor Α ◽

Necrosis Factor

Abstract Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), essential components in the pathogenesis of immunoinflammatory diseases, are strongly induced in monocytes by direct contact with stimulated T lymphocytes. This study demonstrates that adult human serum (HS) but not fetal calf or cord blood serum displays inhibitory activity toward the contact-mediated activation of monocytes by stimulated T cells, decreasing the production of both TNF-α and IL-1β. Fractionation of HS and N-terminal microsequencing as well as electroelution of material subjected to preparative electrophoresis revealed that apolipoprotein A-I (apo A-I), a “negative” acute-phase protein, was the inhibitory factor. Functional assays and flow cytometry analyses show that high-density lipoprotein (HDL)-associated apo A-I inhibits contact-mediated activation of monocytes by binding to stimulated T cells, thus inhibiting TNF-α and IL-1β production at both protein and messenger RNA levels. Furthermore, apo A-I inhibits monocyte inflammatory functions in peripheral blood mononuclear cells activated by either specific antigens or lectins without affecting cell proliferation. These results demonstrate a new anti-inflammatory activity of HDL-associated apo A-I that might have modulating functions in nonseptic conditions. Therefore, because HDL has been shown to bind and neutralize lipopolysaccharide, HDL appears to play an important part in modulating both acute and chronic inflammation. The novel anti-inflammatory function of apo A-I reported here might lead to new therapeutic approaches in inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, and atherosclerosis.

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