Comparative analysis of NK cell subset distribution in normal and lymphoproliferative disease of granular lymphocyte conditions

Abstract

We have characterized the heterogeneity of human blood NK cell subsets defined by expression of KIR, lectin like receptors and NK cell differentiation markers within a cohort of 51 healthy Caucasian individuals. High inter‐individual variability in cell surface expression of most NK cell markers is observed. Range values defining NK cell subsets in healthy donors were further used as references to characterize 14 patients with NK‐type lymphoproliferative disease of granular lymphocytes (NK‐LDGL). Alterations of the KIR repertoire were noted in all NK‐LDGL patients. NK cell expansions were classified as oligoclonal KIR+ or as non‐detectable KIR (ndKIR) using anti‐KIR2DL1/2DS1, anti‐KIR2DL2/2DL3/2DS2, anti‐KIR3DL1 and anti‐KIR2DS4 monoclonal antibodies. A major reduction in the size of the CD56bright NK cell subset was a constant feature of NK‐LDGL. Altered distribution of CD94+, CD161+, and CD162R+ NK cell subsets was also observed in NK‐LDGL patients. Considering the potential role of NK cells in eliminating tumors or virus‐infected cells, the reference values defined in this study should be valuable to characterize both quantitative and qualitative alterations of the NK cell repertoire in pathological conditions and to monitor NK cell reconstitution following hematopoietic transplantation.

Chronic lymphoproliferative disorder of natural killer cells: a distinct entity with subtypes correlating with normal natural killer cell subsets

“…3,5 Although these patterns of NKR expression have been shown to distinguish CLDNKs from normal controls, transient NK cell lymphocytosis with abnormal NKR expression has also been reported; therefore, repeat studies are generally recommended for the confirmation of a CLDNK diagnosis, although the utility of this practice has yet to be formally established. 3,6,7 Functionally and immunophenotypically distinct mature NK cell subsets, often referred to as CD56 bright and CD56 dim NK cells, based on their differential expression of this antigen, have recently been identified. CD56 bright NK cells are found primarily in secondary lymphoid tissues, are brightly NKp46 positive, dimly CD16 positive, have little or no KIR expression and have limited cytotoxic potential, functioning primarily through the elaboration of cytokines, such as interferon-g.…”

“…In normal peripheral blood, NK cell subsets are positive for each of the three tested KIRs, generating a polytypic pattern of KIR expression. 3,6 By comparison, either the uniform lack of KIR expression (UN) or the uniform expression of a single KIR isoform (RES), with or without the expression of another KIR, are both considered abnormal and supportive of a diagnosis of CLDNK. In four study cases, there was a skewed KIR expression without the homocellular staining requisite for KIR restriction; this was considered to be of indeterminate significance for establishing a CLDNK diagnosis.…”

Trispecific killer engager CD16xIL15xCD33 potently induces NK cell activation and cytotoxicity against neoplastic mast cells

“…4-345.6]) compared with that reported in normal donors. 13 No significant differences were noted between SM and SM-AHN NK cells in our small cohort. SM patient NK cells exhibited normal natural cytotoxicity against K562 target cells ( Figure 2B-D …”

Genotypic evaluation of killer immunoglobulin-like receptors in NK-type lymphoproliferative disease of granular lymphocytes

“…[1][2][3] The recent definition of a pattern of surface receptors on the GLs of LDGL patients led to the hypothesis that NK receptors (NKRs) might play a central role in priming GL proliferation in this disease. [4][5][6] Among the NKR family, the killer immunoglobulin-like receptors (KIRs) reportedly related to the susceptibility to NK-type LDGL. [4][5][6] The KIR genes are highly polymorphic and polygenic, 7 the gene content of the KIR cluster varying from individual to individual.…”

“…[4][5][6] Among the NKR family, the killer immunoglobulin-like receptors (KIRs) reportedly related to the susceptibility to NK-type LDGL. [4][5][6] The KIR genes are highly polymorphic and polygenic, 7 the gene content of the KIR cluster varying from individual to individual. 8 KIRs specifically recognize major histocompatibility complex (MHC) class I alleles, including groups of human leukocyte antigen (HLA)-A, HLA-B and HLA-C. 9 Fifteen KIR genes (plus two pseudogenes) have been identified, located on the chromosome 19p13.4 within the leukocyte receptor complex (LCR).…”