The role of stem cell-like memory T cells in systemic lupus erythematosus

Abstract

A novel memory T subset, stem cell-like memory T (Tscm) cell, was recently discovered [1]. Previous studies have shown that Tscm cells can produce their own precursor cells and differentiate into other T cell subsets. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by characteristic systemic inflammatory features caused by immune complex-mediated complement activation. The perpetuation of the autoimmune reaction in this disease suggests the presence of abnormal immune stem cells. In this thesis, I investigated the presence and function of Tscm cells in SLE. The Tscm cells were defined by the presence of the following surface markers: CD3+, CD4+/CD8+, CD45RO-, CCR7+, CD62L+, CD45RA+, CD27+, CD28+, CD127+, CD122+, and CD95hi. The proportions of CD4+ and CD8+ Tscm cells among naïve CD4+ and CD8+ T cells or the total CD4+ and CD8+ T cells were significantly increased in SLE patients compared to those of the healthy controls. Tscm cells from SLE patients can proliferate and renew themselves and differentiate into naïve-like (CD3+, CD4+/CD8+, CD45RO-, CCR7+ and CD45RA+), central memory (CD3+, CD4+/CD8+, CD45RO+, CCR7+, and CD45RA-) and effector memory (CD3+, CD4+/CD8+, CD45RO+, CCR7-, and CD45RA-) T lymphocytes. The stimulated Tscm cells of SLE patients secreted more IFN-γ, TNF-α and IL-2 compared with those from the HCs. Tscm cells from SLE patients can differentiate into Tfh cells, and the differentiated Tfh cells can make B cells to produce antibodies. Tfh cells are induced by Tscm cells through upregulation of IL-21 and downregulation of Blimp-1 which are controlled by the transcription levels of TCF-1. The proportion of Tscm cells showed no association with the SLE disease activity suggesting that Tscm cells determine the development of disease but not the disease activity. Taken together, this study shows that the proportion of Tscm cells is increased in SLE patients and that Tfh cells differentiated from Tscm cells play a role in maintaining SLE by helping B cells produce autoantibodies.