Analysis of immunoglobulin-like transcripts (ILTs) in lymphocytes with sHLA-G and IL10 from SLE patients

The aim of this work was to study the expression of human leukocyte antigen G (HLA-G) and interleukin 10 (IL-10) in conjunction with expression of HLA-G killer-cell inhibitory receptor ligand immunoglobulin-like transcript 2 (ILT2) in CD3+, CD19+, CD56+ lymphomas, and ILT4 in CD14+ cells from patients with systemic lupus erythematosus (SLE). Thirty-one SLE patients and 36 healthy controls were studied. ILTs expression was analyzed by flow cytometry in peripheral blood mononuclear cells (PBMCs). The plasma sHLA-G and IL10 were evaluated by enzyme-linked immunosorbent assay (ELISA). We found a significant increased expression of ILT2 by lymphocytes in SLE patients. When the expression of this receptor was assessed in cell subsets, significantly higher ILT2 MRFI levels were detected in CD3+ cells, CD19+ cells, CD56+ cells (P < 0.05), but no change with ILT4 MRFI in CD14+ cells, neither did the percentages of ILT2/4+ lymphocytes change in SLE patients compared with healthy controls (P > 0.05). The upregulation of ILT2 expression was related to IL10 and anti-ds-DNA antibodies (P < 0.05), but not sHLA-G and steroid therapy (P > 0.05). IL-10 and sHLA-G were increased, but did not change remarkably (P > 0.05); however, they were quite related (P < 0.05). ILT2 might be one of the factors accounting for the evasion of immunosurveillance, thus participate in the pathogenesis of SLE, and the upregulation of ILT2 may be associated with its disease activity.

[1]  J F Fries,et al.  The 1982 revised criteria for the classification of systemic lupus erythematosus. , 1982, Arthritis and rheumatism.

[2]  O. Mandelboim,et al.  Protection from Natural Killer Cell-Mediated Lysis by HLA-G Expression on Target Cells , 1996, Science.

[3]  M. Colonna,et al.  A Common Inhibitory Receptor for Major Histocompatibility Complex Class I Molecules on Human Lymphoid and Myelomonocytic Cells , 1997, The Journal of experimental medicine.

[4]  C. Copie-Bergman,et al.  Human interleukin-10 expression in T/natural killer-cell lymphomas: association with anaplastic large cell lymphomas and nasal natural killer-cell lymphomas. , 1998, The American journal of pathology.

[5]  M. Colonna,et al.  A novel family of Ig‐like receptors for HLA class I molecules that modulate function of lymphoid and myeloid cells , 1999, Journal of leukocyte biology.

[6]  M. Colonna,et al.  The ILT2(LIR1) and CD94/NKG2A NK cell receptors respectively recognize HLA‐G1 and HLA‐E molecules co‐expressed on target cells , 1999, European journal of immunology.

[7]  J. Dausset,et al.  HLA-G-mediated inhibition of antigen-specific cytotoxic T lymphocytes. , 1999, International immunology.

[8]  I. Sargent,et al.  HLA-G suppresses proliferation of CD4(+) T-lymphocytes. , 2000, Journal of reproductive immunology.

[9]  A. Toubert,et al.  Cutting Edge: Soluble HLA-G1 Triggers CD95/CD95 Ligand-Mediated Apoptosis in Activated CD8+ Cells by Interacting with CD81 , 2000, The Journal of Immunology.

[10]  J. Dausset,et al.  Soluble HLA-G protein secreted by allo-specific CD4+ T cells suppresses the allo-proliferative response: A CD4+ T cell regulatory mechanism , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[11]  R. Dummer,et al.  HLA-G protein up-regulation in primary cutaneous lymphomas is associated with interleukin-10 expression in large cell T-cell lymphomas and indolent B-cell lymphomas. , 2002, Blood.

[12]  S. Bruno,et al.  Dual Effect of CD85/Leukocyte Ig-Like Receptor-1/Ig-Like Transcript 2 and CD152 (CTLA-4) on Cytokine Production by Antigen-Stimulated Human T Cells1 , 2002, The Journal of Immunology.

[13]  Siyuan Liang,et al.  Mobilizing dendritic cells for tolerance by engagement of immune inhibitory receptors for HLA-G. , 2003, Human immunology.

[14]  S. Ferrone,et al.  Soluble HLA‐A,‐B,‐C and ‐G molecules induce apoptosis in T and NK CD8+ cells and inhibit cytotoxic T cell activity through CD8 ligation , 2003, European journal of immunology.

[15]  C. Lau,et al.  Pathogenesis of systemic lupus erythematosus , 2003, Journal of clinical pathology.

[16]  R. Dummer,et al.  HLA-G and IL-10 expression in human cancer--different stories with the same message. , 2003, Seminars in cancer biology.

[17]  T. Bellón,et al.  Recruitment of C-terminal Src kinase by the leukocyte inhibitory receptor CD85j. , 2004, Biochemical and biophysical research communications.

[18]  J. Trowsdale,et al.  The LILR family: modulators of innate and adaptive immune pathways in health and disease. , 2004, Tissue antigens.

[19]  G. Aversa,et al.  Interleukin 10 regulates cell surface and soluble LIR‐2 (CD85d) expression on dendritic cells resulting in T cell hyporesponsiveness in vitro , 2004, European journal of immunology.

[20]  J. Pers,et al.  Dysfunctional B cells in systemic lupus erythematosus. , 2004, Autoimmunity reviews.

[21]  Hiroshi Hashimoto,et al.  Extensive polymorphisms of LILRB1 (ILT2, LIR1) and their association with HLA-DRB1 shared epitope negative rheumatoid arthritis. , 2005, Human molecular genetics.

[22]  E. Carosella,et al.  HLA‐G up‐regulates ILT2, ILT3, ILT4, and KIR2DL4 in antigen presenting cells, NK cells, and T cells , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[23]  B. Mordmüller,et al.  Increase in annexin V-positive B cells expressing LILRB1/ILT2/CD85j in malaria. , 2006, European cytokine network.

[24]  R. Loewenthal,et al.  HLA-G levels in serum and plasma. , 2006, Tissue antigens.

[25]  R. González-Amaro,et al.  Analysis of expression and function of the inhibitory receptor ILT2 (CD85j/LILRB1/LIR-1) in peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE). , 2007, Journal of autoimmunity.

[26]  M. Rubini,et al.  HLA-G genotype and HLA-G expression in systemic lupus erythematosus: HLA-G as a putative susceptibility gene in systemic lupus erythematosus. , 2008, Tissue antigens.

[27]  M. Citores,et al.  Expression of human leukocyte antigen-G in systemic lupus erythematosus. , 2008, Human immunology.

[28]  M. Roncarolo,et al.  Role of human leukocyte antigen-G in the induction of adaptive type 1 regulatory T cells. , 2009, Human immunology.

[29]  E. Hauben,et al.  Differentiation of type 1 T regulatory cells (Tr1) by tolerogenic DC-10 requires the IL-10-dependent ILT4/HLA-G pathway. , 2010, Blood.