POS0761\u2005INVESTIGATION ON THE EFFECT AND MECHANISM OF ABNORMALLY ACTIVATED CD8+ T CELLS FROM BONE MARROW ON HEMATOPOIETIC STEM CELLS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Abstract

SLE is an autoimmune disease characterized by the abnormal function of lymphocytes. The impairment of hematopoietic function of bone marrow participates in its pathogenesis, in which T cells play an important role. However, study on bone marrow T cells in SLE patients is very limited.This study aims to characterize the phenotype and molecular characteristics of abnormally activated CD8+T cells in bone marrow of SLE patients and explore the mechanism of hematopoietic stem cells (HSCs) reduction caused by the abnormally activated CD8+T cells in bone marrow of patients with SLE.A total of 8 SLE patients and 5 age- and sex-matched controls were recruited in our study. Among them, 3 SLE patients and 4 donors were collected bone marrow and peripheral blood samples for Single-cell RNA sequencing (scRNA-seq) and functional studies. BM and peripheral T cell subsets were measured by flow cytometry. Plasma cytokines and secreted immunoglobulins were detected by Luminex. Disease activity of SLE patients was measured using the SLE Disease Activity Index (SLEDAI). All analyses were performed using R language and Flowjo 9.In the present study, SLE patients had increased CD8+T%αβT cells and decreased CD4+T%αβT cells in bone marrow of SLE, compared to healthy controls. A large number of CD38+HLADR+CD8+T cells existed in the bone marrow and peripheral blood of SLE patients. Those patients also showed reduced number of HSCs, and with a downward trend of the numbers of peripheral red blood cells, white blood cells, neutrophils, hemoglobin, and platelets. By scRNA-seq, the CD38+HLADR+CD8+T cells contained high levels of GZMK, GZMA, PRF1, IFNG, and TNF in the bone marrow of SLE patients. the CD38+HLADR+CD8+T cells exhibited significant relationship with HSCs, white blood cells, neutrophils, and platelets.These findings demonstrated that the abnormally activated CD8+T cells in bone marrow can reduce the number of HSCs by the expression of killer molecules, which contributes to the impairment of hematopoietic function and the development of SLE. This project focuses on the specific bone marrow T cell subset in SLE. The completement of this project provides information for exploring the mechanism of hematopoiesis involvement.[1]Anderson E, Shah B, Davidson A, Furie R. Lessons learned from bone marrow failure in systemic lupus erythematosus: Case reports and review of the literature. Semin Arthritis Rheum. 2018;48(1):90-104.[2]Sun LY, Zhou KX, Feng XB, Zhang HY, Ding XQ, Jin O, Lu LW, Lau CS, Hou YY, Fan LM. Abnormal surface markers expression on bone marrow CD34+cells and correlation with disease activity in patients with systemic lupus erythematosus. Clin Rheumatol. 2007;26(12):2073-2079.We want to thank Lu Meng, Teng Li, Wei Zhou, and Jiaxin Guo for their assistance with this study.None declared