Tumor necrosis factor is critical for cytolytic T cell activity against allospecific hepatocytes and splenic targets in major histocompatibility complex class I disparate graft versus host disease

Sabina Ali, Ruth Starwalt, Jake Kreck, Bonnie Whittington, Geri R. Brown

Research output: Contribution to journalArticle

Abstract

The present studies determined the role of tumor necrosis factor (TNF)/tumor necrosis factor receptor (TNFR) interactions on cytolytic (CTL) activity of splenic and intrahepatic lymphocytes (IHL) isolated from mice undergoing graft versus host disease, induced by transfer of B6 T cells to major histocompatibility complex (MHC) class I disparate bm1×B6 F1 mice. Allospecific killing of anti-H-2bm1 splenic and hepatocyte targets was assessed by 4-h 51Cr release and 16-h DNA lysis assays, respectively, utilizing spleen cells (SpC) and IHL isolated (1) from sublethally irradiated bm1×B6 F1 who had received B6 spleen and bone marrow cells, and a control adenovirus (Adv-βgal) or a TNF inhibitor expressing adenovirus (Adv-TNFi), or (2) from bm1×B6 F1 recipients of B6, B6.129-Tnfrsf1atm1Mak/J (TNFR1-/-), B6.129S2-Tnfrsf1b tm1Mwm/J (TNFR2-/-), or B6.129S-Tnfrsf1atm1Imx Tnfrsf1btm1Imx/J (TNFR-/-) SpC and bone marrow cells, or (3) from in vitro-activated SpC. Splenic and IHL from bone marrow transplant recipients who had received Adv-TNFi at the time of transplant displayed lower allospecific CTL activity than controls. Addition of TNFR-Ig or a TNF antibody before the CTL activity assay further reduced allospecific killing against bm1 SpC blast targets. Both TNF/TNFR1 and TNF/TNFR2 interactions were critical for the development of optimal CTL activity against allospecific hepatocyte targets. Further, TNFR1- and TNFR2-deficient SpC from MHC class I disparate mixed lymphocyte cultures displayed lower CTL activity and expression of effector molecules than control B6 SpC. TNF/TNFR interactions were critical for the development of optimal CTL activity of IHL and splenic cytotoxic T cells against MHC class I disparate SpC blast and hepatocyte targets in MHC class I disparate graft versus host disease.

Original languageEnglish (US)
Pages (from-to)423-431
Number of pages9
JournalJournal of Interferon and Cytokine Research
Volume31
Issue number5
DOIs
StatePublished - May 1 2011

ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Virology

Fingerprint Dive into the research topics of 'Tumor necrosis factor is critical for cytolytic T cell activity against allospecific hepatocytes and splenic targets in major histocompatibility complex class I disparate graft versus host disease'. Together they form a unique fingerprint.

  • Cite this