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 D.
N1 - Funding Information:
This work was supported by the Mayo Clinic Foundation (to A.C.P. and N.W.C.). S.R.L. was supported by the National Institutes of Health (NIH) Delaney AIDS Research Enterprise (Grants U19 AI096109 and UM1 AI126611-01) and the National Health and Medical Research Council (NHMRC) of Australia (NHMRC program grant and practitioner fellowship). A.D.B. was supported by the National Institute of Allergy and Infectious Diseases of the NIH (Grants AI110173 and AI120698). H.-P.K. is a Markey Molecular Medicine Investigator and received support as the inaugural recipient of the José Carreras/E. Donnall Thomas Endowed Chair for Cancer Research and the Fred Hutch Endowed Chair for Cell and Gene Therapy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
Copyright Ó 2019 by The American Association of Immunologists, Inc.
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 -