Increased expression of non-functional killer inhibitory receptor CD94 in CD8+ cells of myeloma patients

Barbara Besostri, Eloise Beggiato, Alberto Bianchi, Sara Mariani, Marta Coscia, Silvia Peola, Myriam Foglietta, Mario Boccadoro, Alessandro Pileri, Lorenzo Moretta, Massimo Massaia

Research output: Contribution to journalArticlepeer-review

Abstract

Different MHC class I-specific killer inhibitory receptors (KIRs) are expressed in vivo by a minor fraction of activated memory CD8+ cells. It has been postulated that KIRs may 'fine-tune' specific responses by altering their threshold of activation by the TCR-CD3 complex. We have previously shown that, in multiple myeloma (MM) patients, a large fraction of peripheral blood CD8+ cells display the phenotype of chronically activated memory T cells (CD38+, HLA-DR+, CD25-, CD45R0+, CD28-). We investigated the expression of KIRs on MM T cells and determined their possible influence on cytolytic responses elicited via the CD3-TCR complex. The expression of CD94, a molecule that is part of a heterodimeric KIR recognizing the nonclassical MHC surface HLA-E molecule, was almost threefold higher in MM T cells than in age-matched normal control subjects (P <0.0001). CD94 expression was preferentially confined to CD8+ cells but not restricted to activated (HLA- DR+) and/or memory (CD45R0+) T cells. Unlike normal T cells, in which CD94 is assembled with glycoproteins of the NKG2 family to form functional receptors with activating or inhibitory properties, most CD94+ MM T cells were devoid of both the NKG2-A and NKG2-C glycoproteins detected in the inhibitory or activating form respectively. CD94 blockade did not significantly affect either T-cell proliferation or cytotoxic T-lymphocyte generation induced by the myeloma-derived cell lines NCI and RPMI 8226. Similarly, the cytolytic activity induced by direct anti-CD3-mediated targeting of MM T cells to FCR+ P815 target cells was unaffected by the addition of anti-CD94 and/or anti-NKG2-A/C monoclonal antibodies (mAbs). These data indicate that the large majority of MM CD8+ cells do not express a functional CD94 receptor. Thus, their ability to 'fine-tune' an appropriate immune response against tumour cells can be impaired.

Original languageEnglish
Pages (from-to)46-53
Number of pages8
JournalBritish Journal of Haematology
Volume109
Issue number1
DOIs
Publication statusPublished - 2000

Keywords

  • CD94
  • Cytotoxicity
  • Inhibitory receptors
  • Myeloma
  • T lymphocytes

ASJC Scopus subject areas

  • Hematology

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