Phenotypic diversity of natural killer (NK) populations in patients with NK-type lymphoproliferative disease of granular lymphocytes

Abstract

Using monoclonal antibodies (MoAbs) termed GL183 and EB6, directed to a novel family of natural killer (NK) specific triggering molecules, four functional subsets of NK cells have been recently defined (GL183+EB6-; GL183+EB6+; GL183-EB6+; GL183-EB6-). In healthy individuals, all these subsets are represented in variable portion. The expression of EB6 and GL183 surface antigens has been analyzed in a series of 14 patients with lymphoproliferative disease of granular lymphocytes (LDGL) characterized by a chronic CD3-CD16+ lymphocytosis. Our data showed that in 11 of 14 cases, the proliferation was specifically sustained by one of the four possible subsets of granular lymphocytes (GLs) (seven cases: EB6-GL183-; three cases: EB6+GL183-; one case: EB6-GL183+). In the remaining three cases, a pattern was demonstrated that is consistent with that of healthy individuals (ie, the presence of all four subsets). When expressed on GL surfaces, in the majority of cases tested both EB6 and GL183 MoAbs behave as functional surface molecules as assessed in the redirected killing of P815 target cells. We also provided evidence that EB6+GL183+ proliferating cells show a definite (type 1) in vitro NK specificity as do their normal counterparts. The unique expansion of a defined subset of NK cells in most patients with LDGL suggests that the pathologic noxa leading to GL proliferation selectively acts on a specific subset of NK lymphocytes.

Differential expression of CD3 and CD7 in T‐cell malignancies: a quantitative study by flow cytometry

“…It is more difficult to define a specific stage of T-cell maturation of the cells of GLL. It is likely that this disorder is immunologicall y heterogenous (McDaniel et al, 1992;Zambello et al, 1993;Dhodapkar et al, 1994) and that in some cases the granular lymphocytes are activated mature T cells or NK cells. The slightly low CD3 expression that we have documented in some cases could reflect a functional reactive state and not necessarily a marker of cellular immaturity.…”

Deciphering the killer‐cell immunoglobulin‐like receptor system at super‐resolution for natural killer and T‐cell biology

“…For instance, in NK and T-cell large granular lymphocytosis lymphocytes often express activating or inhibitory KIRs in a clonal manner. [225][226][227][228] Patients with Sezary syndrome typically display CD4 + T cells expressing KIR3DL2, which might contribute to disease onset. 228,229 For this reason, KIR are considered as a potential therapeutic target because they are only expressed on a small subset of normal lymphocytes, the deletion of which is unlikely to be harmful.…”

IL‐12 is involved in the activation of CD3+ granular lymphocytes in patients with lymphoproliferative disease of granular lymphocytes

“…Cytotoxic activity. Cytotoxic activity was assessed by the lysis of 51 Cr-labelled K-562 and P815 target cells in a 4 h assay, as already reported (Zambello et al, 1990(Zambello et al, , 1993.…”