Expression and function of NKG2D in CD4+ T cells specific for human cytomegalovirus

Andrea Sáez-Borderías, Mónica Gumá, Ana Angulo, Beatriz Bellosillo, Daniela Pende, Miguel López-Botet

Research output: Contribution to journalArticle

Abstract

The human NKG2D killer lectin-like receptor (KLR) is coupled by the DAP10 adapter to phosphoinositide 3-kinase (P13 K) and specifically interacts with different stress-inducible molecules (i.e. MICA, MICB, ULBP) displayed by some tumour and virus-infected cells. This KLR is commonly expressed by human NK cells as wen as TCRγδ + and TCRαβ+CD8+ T lymphocytes, but it has been also detected in CD4+ T cells from rheumatoid arthritis and cancer patients. In the present study, we analysed NKG2D expression in human cytomegalovirus (HCMV)-specific CD4+ T lymphocytes. In vitro stimulation of peripheral blood mononuclear cells (PBMC) from healthy seropositive individuals with HCMV promoted variable expansion of CD4+NKG2D+ T lymphocytes that coexpressed perforin. NKG2D was detected in CD28- and CD28dull subsets and was not systematically associated with the expression of other NK cell receptors (i.e. KIR, CD94/NKG2 and ILT2). Engagement of NKG2D with specific mAb synergized with TCR-dependent activation of CD4+ T cells, triggering proliferation and cytokine production (i.e. IFN-γ and TNF-α). Altogether, the data support the notion that NKG2D functions as a prototypic costimulatory receptor in a subset of HCMV-specific CD4+ T lymphocytes and thus may have a role in the response against infected HLA class II+ cells displaying NKG2D ligands.

Original languageEnglish
Pages (from-to)3198-3206
Number of pages9
JournalEuropean Journal of Immunology
Volume36
Issue number12
DOIs
Publication statusPublished - Dec 2006

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Keywords

  • Cytomegalovirus
  • GD85j
  • KIR
  • NKG2D
  • T cell

ASJC Scopus subject areas

  • Immunology

Cite this

Sáez-Borderías, A., Gumá, M., Angulo, A., Bellosillo, B., Pende, D., & López-Botet, M. (2006). Expression and function of NKG2D in CD4+ T cells specific for human cytomegalovirus. European Journal of Immunology, 36(12), 3198-3206. https://doi.org/10.1002/eji.200636682