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.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Casado
L F
LF
Servicio de Hematología y Hemoterapia, Hospital Virgen de la Salud, Avenida de Barber 30, Toledo, Spain. lcasado@cht.insalud.es
Granados
E
E
Algara
P
P
Navarro
F
F
Martinez-Frejo
M C
MC
López-Botet
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D002999:Clone Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D015395:Histocompatibility Antigens Class I; D006801:Humans; D007945:Leukemia, Lymphoid / Q000378:metabolism / Q000473:pathology*; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008297:Male; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000378:metabolism*
D015703:Antigens, CD; D015395:Histocompatibility Antigens Class I; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic