High expression of the ILT2 (LIR-1) inhibitory receptor for major histocompatibility complex class i molecules on clonal expansions of T large granular lymphocytes in asymptomatic patients
Casado, L.F.; Granados, E.; Algara, P.; Navarro, F.; Martinez-Frejo, M.C.; López-Botet, M.
Haematologica 86(5): 457-463
2001
ISSN/ISBN: 0390-6078 PMID: 11410407 Document Number: 540229
The lymphoproliferative disorders of large granular lymphocytes (LGLD) are divided into two groups: T-cell type and NK-cell type. These entities may be either asymptomatic or associated with autoimmune manifestations (especially cytopenias). A number of surface receptors, expressed by NK-cells and some T-lymphocyte subsets repress cytotoxicity and cytokine production upon ligation with HLA class I molecules and are clonally expressed in theses lymphoproliferative disorders. These cytotoxic lymphocytes can lyse erythroid progenitors in vitro, and the physiologic lower levels of HLA class I antigens on the erythroid lineage may contribute to this form of autoimmunity. It is conceivable that the clinical outcome of T-LGLD might be influenced by the expression of MHC class I inhibitory receptors. We analyzed the surface expression of these molecules, lectin-like heterodimers (CD94/NKG2A) or killer immunoglobulin (Ig)-like receptors (KIR) and another Ig-like inhibitory receptor, termed ILT2 or LIR-1 in CD8+ cells from 12 cases of ab T-LGLD using specific monoclonal antibodies. None of the LGLD cases had anemia and 11 of 12 patients remain asymptomatic. KIR and CD94/NKG2A expression was detected on CD8+ populations only in some cases of T-LGLD. By contrast, our observations revealed that ILT2 expression was markedly higher in CD8+ cells from LGLD patients than from healthy donors. Expression of the ILT2 inhibitory receptor for HLA class I molecules on LGLD cells might indeed contribute to preventing their autoreactivity. Further studies are required to evaluate the expression/function of the ILT2 receptor in patients who eventually become symptomatic. The development of cytopenias in LGLD patients must involve other self-reactive activating receptors. Analysis of the expression and function of triggering NKR in LGLD needs to be carefully addressed.