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During HIV infection, CD4 T cells in lymphoid tissues initiate a highly
inflammatory form of cell death that helps cripple the immune system.
The activation of a helper T cell and its roles in immunity
Phagocytic cell
(yellow) engulfing
a foreign cell
Self-nonself
complex
Macrophage
Microbe
B cell
T cell
receptor
Interleukin-2
stimulates
cell division
5
3
1
2
Helper
T cell
4
6
7
Interleukin-2
activates B cells
and other T cells
Self protein
Antigen from the microbe
(nonself molecule)
Antigen-presenting
cell
Binding
site for the
self protein
Interleukin-1
stimulates the
helper T cell Binding
site for the
antigen
Humoral
immune
response
(secretion of
antibodies by
plasma cells)
Cytotoxic
T cell
Cell-mediated
immune
response
(attack on
infected cells)
How HIV Destroys Immune Cells?
For years we’ve just said ‘HIV infects the cells and kills them,’ but it’s clearly
more complicated than that.
Productively infected by HIV, meaning that the virus has integrated with hostcell genome and can make copies of itself (death occurs through apoptosis
mediated by an enzyme called caspase-3).
In a 2010 study, Greene and his colleagues showed that 95 percent of CD4 T
cells in lymphoid tissue, by contrast, are bystander cells that are “abortively
infected”--- the virus penetrates but can’t integrate or replicate (death occurs
by pyroptosis, which depends on the activation of caspase-1).
Proinflammatory signals released by pyroptosis attract more cells into the
infected tissue to die and, in turn, produce more inflammation.
細胞焦亡
細胞凋亡
Pyroptosis is a form of programmed cell death associated with antimicrobial
responses during inflammation. In contrast to apoptosis, pyroptosis requires the
function of caspase-1.
IFI16 DNA Sensor Is Required for Death of Lymphoid CD4 T Cells Abortively
Infected with HIV
Interferon-gamma–inducible protein 16 (IFI16)
Pyroptosis in HIV-infected lymphoid tissues may establish a chronic cycle of CD4 T-cell death and
inflammation, which attracts new CD4 T cells and ultimately contributes to disease progression and tissue
damage. Inhibitors of caspase 1 such as VX-765 may inhibit pyroptosis in a manner that both preserves
CD4 T cells and reduces inflammation.
Pyroptosis---a highly inflammatory form of cell death that lures more CD4
T cells to the area, thereby creating a vicious cycle that ultimately wreaks
havoc on the immune system.
IFI16, which is known to be part of the protein complex that initiates
inflammatory immune responses.
An existing caspase-1 inhibitor---a drug already shown to be safe in
humans;;uppressed CD4 T-cell death and inflammation in cell culture.
A technique called DNA affinity chromatography to identify proteins in the
CD4 T cells that detect fragments of HIV DNA and alert the enzyme caspase-1.
Caspase-1 inhibitors might—and I emphasize might—become a component of
a curative cocktail.”