Abstract
CD4 T cells from HIV-1 infected patients die at excessive rates compared to those from uninfected patients, causing immunodeficiency. We previously identified a dominant negative ligand that antagonizes the TRAIL-dependent pathway of cell death, which we called TRAILshort. Because the TRAIL pathway has been implicated in CD4 T cell death occurring during HIV-1 infection, we used short hairpin RNA knockdown, CRISPR deletion, or Abs specific for TRAILshort to determine the effect of inhibiting TRAILshort on the outcome of experimental acute HIV infection in vitro. Strikingly, all three approaches to TRAILshort deletion/inhibition enhanced HIV-induced death of both infected and uninfected human CD4 T cells. Thus, TRAILshort impacts T cell dynamics during HIV infection, and inhibiting TRAILshort causes more HIV-infected and uninfected bystander cells to die. TRAILshort is, therefore, a host-derived, host-adaptive mechanism to limit the effects of TRAIL-induced cell death. Further studies on the effects of TRAILshort in other disease states are warranted. The Journal of Immunology, 2019, 203: 718–724.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 718-724 |
| Number of pages | 7 |
| Journal | Journal of Immunology |
| Volume | 203 |
| Issue number | 3 |
| DOIs | |
| State | Published - Aug 1 2019 |
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ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
Trailshort protects against CD4 T cell death during acute HIV infection. / Natesampillai, Sekar; Paim, Ana C.; Cummins, Nathan W; Chandrasekar, Aswath P.; Bren, Gary D.; Lewin, Sharon R.; Kiem, Hans Peter; Badley, Andrew David.
In: Journal of Immunology, Vol. 203, No. 3, 01.08.2019, p. 718-724.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Trailshort protects against CD4 T cell death during acute HIV infection
AU - Natesampillai, Sekar
AU - Paim, Ana C.
AU - Cummins, Nathan W
AU - Chandrasekar, Aswath P.
AU - Bren, Gary D.
AU - Lewin, Sharon R.
AU - Kiem, Hans Peter
AU - Badley, Andrew David
PY - 2019/8/1
Y1 - 2019/8/1
N2 - CD4 T cells from HIV-1 infected patients die at excessive rates compared to those from uninfected patients, causing immunodeficiency. We previously identified a dominant negative ligand that antagonizes the TRAIL-dependent pathway of cell death, which we called TRAILshort. Because the TRAIL pathway has been implicated in CD4 T cell death occurring during HIV-1 infection, we used short hairpin RNA knockdown, CRISPR deletion, or Abs specific for TRAILshort to determine the effect of inhibiting TRAILshort on the outcome of experimental acute HIV infection in vitro. Strikingly, all three approaches to TRAILshort deletion/inhibition enhanced HIV-induced death of both infected and uninfected human CD4 T cells. Thus, TRAILshort impacts T cell dynamics during HIV infection, and inhibiting TRAILshort causes more HIV-infected and uninfected bystander cells to die. TRAILshort is, therefore, a host-derived, host-adaptive mechanism to limit the effects of TRAIL-induced cell death. Further studies on the effects of TRAILshort in other disease states are warranted. The Journal of Immunology, 2019, 203: 718–724.
AB - CD4 T cells from HIV-1 infected patients die at excessive rates compared to those from uninfected patients, causing immunodeficiency. We previously identified a dominant negative ligand that antagonizes the TRAIL-dependent pathway of cell death, which we called TRAILshort. Because the TRAIL pathway has been implicated in CD4 T cell death occurring during HIV-1 infection, we used short hairpin RNA knockdown, CRISPR deletion, or Abs specific for TRAILshort to determine the effect of inhibiting TRAILshort on the outcome of experimental acute HIV infection in vitro. Strikingly, all three approaches to TRAILshort deletion/inhibition enhanced HIV-induced death of both infected and uninfected human CD4 T cells. Thus, TRAILshort impacts T cell dynamics during HIV infection, and inhibiting TRAILshort causes more HIV-infected and uninfected bystander cells to die. TRAILshort is, therefore, a host-derived, host-adaptive mechanism to limit the effects of TRAIL-induced cell death. Further studies on the effects of TRAILshort in other disease states are warranted. The Journal of Immunology, 2019, 203: 718–724.
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U2 - 10.4049/jimmunol.1900271
DO - 10.4049/jimmunol.1900271
M3 - Article
C2 - 31189571
AN - SCOPUS:85069615300
VL - 203
SP - 718
EP - 724
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 3
ER -