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

Background and Objectives. The lymphoproliferative disorders of large granu lar lymphocytes (LGLD) are divided into two groups: T-cell type and NK-cell type, These entities may be either asymptomatic or associated with autoimm une manifestations (especially cytopenias), A number of surface receptors, expressed by NK-cells and some T-lymphocyte subsets repress cytotoxicity an d cytokine production upon ligation with HLA class I molecules and are clon ally expressed in theses lymphoproliferative disorders. These cytotoxic lym phocytes can lyse erythroid progenitors in vitro, and the physiologic lower levels of HLA class 1 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 1 inhibitory recep tors. Design and Methods. We analyzed the surface expression of these molecules, lectin-like heterodimers (CD94/NKG2A) or killer immuoglobulin (Ig)-like rec eptors (KIR) and another Ig-like inhibitory receptor, termed ILT2 or LIR-1 in CD8(+) cells from 12 cases of alpha beta T-LGLD using specific monoclona l antibodies. Results. None of the LGLD cases had anemia and 11 of 12 patients remain asy mptomatic. 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. Interpretation and Conclusions. expression of the ILT2 inhibitory receptor for HLA class I molecules on LGLD cells might indeed contribute to preventi ng their autore-activity. Further studies are required to evaluate the expr ession/function of the ILT2 receptor in patients who eventually become symp tomatic. 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. (C) 2001, Ferra ta Storti Foundation.