Regulation of γδ T cell survival by soluble HLA-I: Involvement of CD8 and activating killer Ig-like receptors

Alessando Poggi, Paola Contini, Silvia Catellani, Maurizio Setti, Giuseppe Murdaca, Maria Raffaella Zocchi

Research output: Contribution to journalArticlepeer-review

Abstract

We show that human Vδ1 or Vδ2 T lymphocytes secrete FasL and undergo apoptosis upon incubation with soluble HLA (sHLA)-I or after cross-linking of CD8, with a kinetics different from that observed following ligation of TCR. sHLA-I-induced apoptosis was blocked by anti-CD8 mAb; on the other hand, sHLA-I was not effective in CD8- clones, while an HLA-I mutated in the α3 domain, responsible for CD8 binding, was not functional on CD8+ clones. Purified sHLA-Cw3 or -Cw4 alleles, isolated from the Cw3-or Cw4-transfected 721.221 lymphoblastoid cell line, triggered γδ T cell apoptosis, interacting with the specific receptors CD158j/KIR2DS2 or CD158 h/KIR2DS1, respectively, also known as activating isoforms of killer Ig-like receptors (KIR). Again, this effect was dependent on FasL secretion and it was blocked by specific mAb to KIR2DS2 or KIR2DS1. The engagement of CD8 or activating KIR also triggered the production of TNF-α. Noteworthy, sHLA-I molecules synergize with antigen-mediated activation of Vδ2 T cells: Indeed, Vδ2 T lymphocytes produced TNF-α when stimulated with isopentenyl pyrophosphate, and this effect was enhanced by sHLA-I. These findings suggest that sHLA-I can regulate γδ T cell survival and that activating KIR may amplify antigen-specific Vδ2 T cell responses.

Original languageEnglish
Pages (from-to)2670-2678
Number of pages9
JournalEuropean Journal of Immunology
Volume35
Issue number9
DOIs
Publication statusPublished - Sep 2005

Keywords

  • γδ T cells
  • Activating IRS
  • Apoptosis
  • CD8
  • Soluble HLA-I

ASJC Scopus subject areas

  • Immunology

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