Journal Article

Expansion of invariant natural killer T cells from systemic lupus erythematosus patients by alpha-Galactosylceramide and IL-15

Lee, Pei-Tzu, Hsu, Chien-Ya, Kuo, Ming-Ling, Hsiao, Hsiu-Shan, Huang, Jing-Long, Lin, Syh-Jae, Chueh, Yu-Shan

2021

Overview

CD1d-restricted invariant natural killer T cells (iNKT cells) may play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Interleukin (IL)-15 is a pro-inflammatory cytokine which is over-expressed in SLE patients. In the present study, we investigated the iNKT cell expansion of mononuclear cells (MNCs) from SLE patients following 10 days’ culture with α-galactosylceramide (α-Galcer) and /or IL-15. We sought to determine the phenotypic and functional characteristics of the expanded iNKT cells compared to healthy controls and correlated with disease activity. We observed that 1. The percentages of Vα24+/Vβ11+ iNKT cells following 10-day incubation was lower in SLE groups compared to controls; 2. The percentages and absolute numbers of Vα24+/Vβ11+ iNKT cells were expanded by α-galactosylceramide (α-Galcer), and further enhanced with IL-15 in SLE patient, but the effect of IL-15 was much lower than controls; 3.IL-15 +α-Galcer expanded CD3+/CD56+ NKT-like cells from SLE patients, especially with active disease 4. The CD161+ Vα24+/Vβ11+ iNKT cells in SLE were more responsive to α-Galcer stimulation than the CD161- counterpart; 5. IL-15 decreased apoptosis of α-Galcer activated SLE iNKT cells; 6. IL-15 enhanced CD69, CD1d and CD11a expression on α-Galcer treated iNKT cells; 7. The IL-4 production of iNKT cells was decreased in SLE patients compared to controls; 8. IL-15 increased IFN-γ and IL-4 production of SLE iNKT cells; 8. IL-15 failed to augment the ability of iNKT cells to aid NK-mediated K562 cytolysis in SLE patients; 9. CD161 positivity, granzyme B and perforin expression of α-Galcer+IL-15 expanded iNKT cells correlated with C3 levels in SLE patients. Taken together, our results demonstrated numeric and functional deficiency of iNKT cells and their response to IL-15 in SLE patients. Our finding may provide insight for using adoptive iNKT cell therapy in autoimmune diseases.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Alpha galactosidases / Apoptosis / Asthma / Authorship / Autoimmune diseases / Biology and Life Sciences / Blood & organ donations / CD11a antigen / CD1d antigen / CD3 antigen / CD56 antigen / CD69 antigen / Cell culture / Cell therapy / Cells, Cultured / Chronic conditions / Cytokines / Cytolysis / Cytotoxicity / Diagnosis / Female / Flow cytometry / Galactosylceramide / Galactosylceramides - immunology / Granzyme B / Health aspects / Hospitals / Humans / Immunology / Inflammation / Interleukin 15 / Interleukin 4 / Interleukin-15 - immunology / Interleukins / Invariants / Leukocytes (mononuclear) / Lupus / Lupus Erythematosus, Systemic - immunology / Lupus Erythematosus, Systemic - pathology / Lymphocytes / Lymphocytes T / Male / Medical schools / Medicine / Medicine and Health Sciences / Middle Aged / Monoclonal antibodies / Natural killer cells / Natural Killer T-Cells - immunology / Natural Killer T-Cells - pathology / Pathogenesis / Pediatrics / Perforin / Research and Analysis Methods / Rheumatology / Systemic lupus erythematosus / T cells / Young Adult / γ-Interferon