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- Title
Increased expression of non-functional killer inhibitory receptor CD94 in CD8<sup>+</sup> cells of myeloma patients.
- Authors
Besostri, Barbara; Beggiato, Eloise; Bianchi, Alberto; Mariani, Sara; Coscia, Marta; Peola, Silvia; Foglietta, Myriam; Boccadoro, Mario; Pileri, Alessandro; Moretta, Lorenzo; Massaia, Massimo
- 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 non-classical 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.
- Subjects
MULTIPLE myeloma; GLYCOPROTEINS; T cells; CYTOLOGY; PATIENTS
- Publication
British Journal of Haematology, 2000, Vol 109, Issue 1, p46
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1046/j.1365-2141.2000.01981.x