CD8+ tumor-infiltrating lymphocytes are primed for Fas-mediated activation-induced cell death but are not apoptotic in situ

The Journal of Immunology : Official Journal of the American Association of Immunologists
S RadojaAlan B Frey

Abstract

Induction of Fas-mediated activation-induced cell death in antitumor T cells has been hypothesized to permit tumor escape from immune destruction. Several laboratories have proposed that expression of Fas ligand (L) by tumor is the basis for this form of T cell tolerance. In this study, we characterized murine tumor-infiltrating lymphocytes (TIL) for activation status, cell cycle status, level of apoptosis, cytokine secretion, and proliferative capacity. TILs express multiple activation markers (circa CD69, CD95L, CD122, and LFA-1) and contain IL-2 and IFN-gamma mRNAs, but are neither cycling nor apoptotic in situ. In addition, TIL are dramatically suppressed in proliferative response and do not secrete IL-2 and IFN-gamma. However, upon purification and activation in vitro, TIL secrete high levels of IL-2 and IFN-gamma, enter S phase, and then die by Fas-mediated apoptosis. Activation by injection of anti-TCR Ab or IL-2 into tumor-bearing mice induced TIL entrance into S phase preceding apoptosis, showing that TIL have functional TCR-mediated signal transduction in situ. Our data demonstrate that TIL, not tumor, express both Fas and FasL, are arrested in G(1), do not secrete cytokine in situ, and, upon activation in vitro and i...Continue Reading

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Citations

Apr 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sergei Kusmartsev, Dmitry I Gabrilovich
Feb 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mythili KoneruAlan B Frey
May 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mythili KoneruAlan B Frey
Nov 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mehmet O KilincNejat K Egilmez
Aug 2, 2007·Cancer Immunology, Immunotherapy : CII·Heriberto Prado-GarciaJose Sullivan Lopez-Gonzalez
Aug 3, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yan-Yan LiuZuo-Hua Feng
Dec 4, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Edwin J Vazquez-CintronAlan B Frey
Oct 24, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·S RadojaA B Frey
Apr 13, 2005·The Journal of Experimental Medicine·Vincenzo BronteAntonella Viola
Jun 21, 2005·The Journal of Clinical Investigation·Güllü GörgünJohn G Gribben
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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis