Expression and function of KIR and natural cytotoxicity receptors in NK-type lymphoproliferative diseases of granular lymphocytes.
Using monoclonal antibodies (mAbs) specific for different natural killer (NK) receptors, we studied the lymphocyte population from 18 patients with NK-type lymphoproliferative disease of granular lymphocytes (LDGL). The analysis of both resting and cultured NK cell populations demonstrated that these patients are frequently characterized by NK cells displaying a homogeneous staining with given anti-killer Ig-like receptor (anti-KIR) mAb (11 of 18 patients). In most patients NK cells were characterized by the CD94/NKG2A+ phenotype, whereas only a minor fraction of the cases expressed CD94/NKG2C. In 7 of these patients we could also assess the function of the various NK receptors. Remarkably those KIR molecules that, in each patient, homogeneously marked the NK cell expansion were found to display an activating function as determined by cross-linking with specific anti-KIR mAb. The KIR genotype analysis performed in 13 of 18 cases revealed that in NK-type LDGL certain activating KIRs, as well as certain infrequent KIR genotypes, were detected with higher frequencies as compared to previously analyzed healthy donors. Moreover, most KIR genotypes included multiple genes coding for activating KIRs. The analysis of non-HLA-specific triggering receptors indicated that the natural cytotoxicity receptors (NKp46, NKp30) were expressed at significantly low levels in freshly drawn NK cells from most patients analyzed. However, in most instances the expression of NKp46 and NKp30 could be up-regulated on culture in interleukin 2. Our data indicate that in NK-LDGL the expanded subset is frequently characterized by the expression of a given activating KIR, suggesting a direct role for these molecules in the pathogenetic mechanisms of this disorder.
Dipartimento di Medicina Sperimentale, Immunologia Clinica, Università di Padova e Centro di Eccellenza per la Ricerca Biomedica Padova, Padua, Italy.
Renato
R
Zambello
Michela
M
Falco
Mariella
M
Della Chiesa
Livio
L
Trentin
Davide
D
Carollo
Roberta
R
Castriconi
Giovanna
G
Cannas
Simona
S
Carlomagno
Anna
A
Cabrelle
Thierry
T
Lamy
Carlo
C
Agostini
Alessandro
A
Moretta
Gianpietro
G
Semenzato
Massimo
M
Vitale
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000235:genetics; D002460:Cell Line; D005260:Female; D015870:Gene Expression / Q000276:immunology; D020869:Gene Expression Profiling; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007694:Killer Cells, Natural / Q000502:physiology*; D037181:Lectins, C-Type / Q000235:genetics; D008232:Lymphoproliferative Disorders / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D051920:NK Cell Lectin-Like Receptor Subfamily D; D055627:Natural Cytotoxicity Triggering Receptor 1; D055628:Natural Cytotoxicity Triggering Receptor 3; D011971:Receptors, Immunologic / Q000235:genetics*; D054340:Receptors, KIR
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D006680:HLA Antigens; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; C112260:NCR1 protein, human; C431710:NCR3 protein, human; D051920:NK Cell Lectin-Like Receptor Subfamily D; D055627:Natural Cytotoxicity Triggering Receptor 1; D055628:Natural Cytotoxicity Triggering Receptor 3; D011971:Receptors, Immunologic; D054340:Receptors, KIR