Dysregulated NK receptor expression in patients with lymphoproliferative disease of granular lymphocytes.
The natural killer (NK) type of lymphoproliferative disease of granular lymphocytes (LDGL) is associated with the expansion of CD3(-), CD16(+), and/or CD56(+) lymphocytes. We have examined the repertoire of NK receptors expressed on these cells and delineated the functional activity. We found skewed NK receptor expression on patient NK cells. Reactivity to a single anti-killer cell immunoglobulin-like receptor (anti-KIR) antibody was noted in 7 of 13 patients. LDGL patients variably expressed NKp30, NKp44, and NKp46 RNA. In contrast, CD94 and its inhibitory heterodimerization partner NKG2A were homogeneously expressed at high levels on these NK cells. Interestingly, these patients expressed a large number of activating KIR receptors by genotype analysis. Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated that lower than normal levels of RNA of the inhibitory KIR was present in some patients in contrast to normal NK cells. Consistent with a high level of activating receptors, we found the NK-LDGL cells have potent cytolytic function in both direct and redirected cytotoxicity assays. These results demonstrate that patients with NK-LDGL have an increased activating-to-inhibitory KIR ratio. This altered ratio might induce inappropriate lysis or cytokine production and impact the disease pathogenesis.
Epling-Burnette
Pearlie Kay
PK
Department of Interdisciplinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, and James A. Haley Veterans' Administration Hospital, Tampa, FL 33612, USA. burnetpk@moffitt.usf.edu
Painter
Jeffrey S
JS
Chaurasia
Pratima
P
Bai
Fanqi
F
Wei
Sheng
S
Djeu
Julie Y
JY
Loughran
Thomas P
TP
D015703:Antigens, CD / Q000032:analysis; D016022:Case-Control Studies; D003602:Cytotoxicity, Immunologic; D005838:Genotype; D006098:Granulocytes / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology*; D037181:Lectins, C-Type / Q000032:analysis; D008232:Lymphoproliferative Disorders / Q000276:immunology / Q000473:pathology*; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D055627:Natural Cytotoxicity Triggering Receptor 1; D055629:Natural Cytotoxicity Triggering Receptor 2; D055628:Natural Cytotoxicity Triggering Receptor 3; D012333:RNA, Messenger / Q000032:analysis; D011971:Receptors, Immunologic / Q000032:analysis*; D055607:Receptors, Natural Killer Cell
D015703:Antigens, CD; C527054:KLRC1 protein, human; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; C112260:NCR1 protein, human; C112837:NCR2 protein, human; C431710:NCR3 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D055627:Natural Cytotoxicity Triggering Receptor 1; D055629:Natural Cytotoxicity Triggering Receptor 2; D055628:Natural Cytotoxicity Triggering Receptor 3; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell