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Prepublished online as a Blood First Edition Paper on May 15, 2003; DOI 10.1182/blood-2002-12-3898.
Submitted December 24, 2002
Accepted May 1, 2003
Expression and function of KIR and natural cytotoxicity receptors in NK-type lymphoproliferative diseases of granular lymphocytes (LDGL)
Renato Zambello, Michela Falco, Mariella Della Chiesa, Livio Trentin, Davide Carollo, Roberta Castriconi, Giovanna Cannas, Simona Carlomagno, Anna Cabrelle, Thierry Lamy, Carlo Agostini, Alessandro Moretta*, Gianpietro Semenzato, and Massimo Vitale
Dipartimento di Medicina Clinica e Sperimentale, University of Padova and centro di Eccellenza per la Ricerca Biomedica, Padova, Italy
Ist. G. Gaslini, Genova, Italy
DIMES, University of Genova, Genova, Italy; Centro di Eccellenza per la Ricerca Biomedica, University of Genova, Genova, Italy
University of Rennes, Rennes, France
IST - Istituto Scientifico per la Ricerca sul Cancro, Genova, Italy
* Corresponding author; email: alemoret{at}unige.it.
Using mAb specific for different NK receptors we studied the lymphocyte population from 18 patients with NK-type 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-KIR mAb (11 out of 18 cases). In most patients NK cells were characterized by the CD94/NKG2A+ phenotype while only a minor fraction of the cases expressed CD94/NKG2C. In seven 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 crosslinking with specific anti-KIR mAb. The KIR genotype analysis performed in 13 out of 18 cases revealed that in NK type LDGL certain activating KIR, 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 upon culture in IL2. 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.
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