Trailshort protects against CD4 T cell death during acute HIV infection

Sekar Natesampillai, Ana C. Paim, Nathan W Cummins, Aswath P. Chandrasekar, Gary D. Bren, Sharon R. Lewin, Hans Peter Kiem, Andrew David Badley

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)718-724
Number of pages7
JournalJournal of Immunology
Volume203
Issue number3
DOIs
StatePublished - Aug 1 2019

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HIV Infections
Cell Death
T-Lymphocytes
HIV-1
Clustered Regularly Interspaced Short Palindromic Repeats
HIV
Allergy and Immunology
Small Interfering RNA
Ligands

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 journalArticle

Natesampillai, S, Paim, AC, Cummins, NW, Chandrasekar, AP, Bren, GD, Lewin, SR, Kiem, HP & Badley, AD 2019, 'Trailshort protects against CD4 T cell death during acute HIV infection', Journal of Immunology, vol. 203, no. 3, pp. 718-724. https://doi.org/10.4049/jimmunol.1900271
Natesampillai S, Paim AC, Cummins NW, Chandrasekar AP, Bren GD, Lewin SR et al. Trailshort protects against CD4 T cell death during acute HIV infection. Journal of Immunology. 2019 Aug 1;203(3):718-724. https://doi.org/10.4049/jimmunol.1900271
Natesampillai, Sekar ; Paim, Ana C. ; Cummins, Nathan W ; Chandrasekar, Aswath P. ; Bren, Gary D. ; Lewin, Sharon R. ; Kiem, Hans Peter ; Badley, Andrew David. / Trailshort protects against CD4 T cell death during acute HIV infection. In: Journal of Immunology. 2019 ; Vol. 203, No. 3. pp. 718-724.
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