1. During HIV infection, CD4 T cells in lymphoid tissues initiate a highly inflammatory form of cell death that helps cripple the immune system.

2. The activation of a helper T cell and its roles in immunity
Antigen from the microbe (nonself molecule)
Antigen-presenting cell
Self protein
Microbe
Macrophage 1 2 3 4 5 6 7
Self-nonself complex
Phagocytic cell (yellow) engulfing a foreign cell
T cell receptor
Interleukin-1 stimulates the helper T cell
Helper T cell
Binding site for the antigen
Binding site for the self protein
Interleukin-2 stimulates cell division
B cell
Cytotoxic T cell
Interleukin-2 activates B cells and other T cells
Cell-mediated immune response (attack on infected cells)
Humoral immune response (secretion of antibodies by plasma cells)

3. 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 host-cell 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.

4. 細胞焦亡
細胞凋亡
The molecular mechanisms underlying pyroptosis are still poorly defined. Morphologically, pyroptotic cells are characterized by the early loss of plasma membrane integrity77, and this is accompanied by the shedding of membrane vesicles93. Pyroptotic and apoptotic cells share several prominent features (shown in blue boxes), including nuclear condensation and internucleosomal DNA fragmentation, cleavage of the DNA damage repair enzyme poly(ADP-ribose) polymerase 1 (PARP1) and activation of the executioner caspases caspase 3 and caspase 7 (Ref. 45). However, the volume of the cytoplasmic compartment of pyroptotic cells increases, whereas apoptosis is characterized by general shrinkage of the cell volume. Together with the role of caspase 1 in cytokine maturation and unconventional protein secretion, the release of the cytoplasmic content into the extracellular milieu during pyroptosis is thought to render this form of cell death inherently pro-inflammatory45. By contrast, apoptosis is usually considered to be immunologically silent because the cytoplasmic content is packaged in apoptotic bodies and these membrane-bound cell fragments are rapidly phagocytosed in vivo by neighbouring cells and resident phagocytes47. HMGB1, high mobility group box 1; IL, interleukin.

5. 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.

6. IFI16 DNA Sensor Is Required for Death of Lymphoid CD4 T Cells Abortively Infected with HIV
Interferon-gamma–inducible protein 16 (IFI16)

7. 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.

8. 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.”