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

被引:15
作者
Besostri, B
Beggiato, E
Bianchi, A
Mariani, S
Coscia, M
Peola, S
Foglietta, M
Boccadoro, M
Pileri, A
Moretta, L
Massaia, M
机构
[1] Univ Turin, Azienda Osped San Giavanni Battista Torino, Div Ematol, I-10126 Turin, Italy
[2] Ist Nazl Ric Canc, I-16132 Genoa, Italy
[3] Ctr Biotecnol Avanzate, Genoa, Italy
[4] Univ Genoa, Dipartimento Med Sperimentale, Genoa, Italy
关键词
myeloma; inhibitory receptors; T lymphocytes; CD94; cytotoxicity;
D O I
10.1046/j.1365-2141.2000.01981.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:46 / 53
页数:8
相关论文
共 38 条
[1]  
Bakker ABH, 1998, J IMMUNOL, V160, P5239
[2]  
Bertone S, 1999, EUR J IMMUNOL, V29, P23, DOI 10.1002/(SICI)1521-4141(199901)29:01<23::AID-IMMU23>3.0.CO
[3]  
2-Y
[4]  
Bianchi A, 1997, BRIT J HAEMATOL, V97, P815
[5]   Clinical and immunological studies in advanced cancer patients sequentially treated with anti CD3 monoclonal antibody (OKT3) and interleukin-2 [J].
Borrione, P ;
Montacchini, L ;
Beggiato, E ;
Pileri, A ;
Bianchi, A ;
Massaia, M .
LEUKEMIA & LYMPHOMA, 1996, 21 (3-4) :325-330
[6]   HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C [J].
Braud, VM ;
Allan, DSJ ;
O'Callaghan, CA ;
Söderström, K ;
D'Andrea, A ;
Ogg, GS ;
Lazetic, S ;
Young, NT ;
Bell, JI ;
Phillips, JH ;
Lanier, LL ;
McMichael, AJ .
NATURE, 1998, 391 (6669) :795-799
[7]  
Cantoni C, 1998, EUR J IMMUNOL, V28, P327, DOI 10.1002/(SICI)1521-4141(199801)28:01<327::AID-IMMU327>3.0.CO
[8]  
2-O
[9]   Expression of HLA class I-specific inhibitory natural killer cell receptors in HIV-specific cytolytic T lymphocytes: Impairment of specific cytolytic functions [J].
DeMaria, A ;
Ferraris, A ;
Guastella, M ;
Pilia, S ;
Cantoni, C ;
Polero, L ;
Mingari, MC ;
Bassetti, D ;
Fauci, AS ;
Moretta, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (19) :10285-10288
[10]  
DIANZANI U, 1988, BLOOD, V72, P1064