Lymphopenia, Lymphopenia-Induced Proliferation, and Autoimmunity

Abstract

Immune homeostasis is a tightly regulated system that is critical for defense against invasion by foreign pathogens and protection from self-reactivity for the survival of an individual. How the defects in this system might result in autoimmunity is discussed in this review. Reduced lymphocyte number, termed lymphopenia, can mediate lymphopenia-induced proliferation (LIP) to maintain peripheral lymphocyte numbers. LIP not only occurs in normal physiological conditions but also correlates with autoimmunity. Of note, lymphopenia is also a typical marker of immune aging, consistent with the fact that not only the autoimmunity increases in the elderly, but also autoimmune diseases (ADs) show characteristics of immune aging. Here, we discuss the types and rates of LIP in normal and autoimmune conditions, as well as the coronavirus disease 2019 in the context of LIP. Importantly, although the causative role of LIP has been demonstrated in the development of type 1 diabetes and rheumatoid arthritis, a two-hit model has suggested that the factors other than lymphopenia are required to mediate the loss of control over homeostasis to result in ADs. Interestingly, these factors may be, if not totally, related to the function/number of regulatory T cells which are key modulators to protect from self-reactivity. In this review, we summarize the important roles of lymphopenia/LIP and the Treg cells in various autoimmune conditions, thereby highlighting them as key therapeutic targets for autoimmunity treatments.

Relationship Between C-Reactive Protein/Serum Albumin Ratio, Neutrophil/Lymphocyte Ratio, and ANCA-Associated Vasculitis Activity: A Retrospective Single Center Cohort Study

“…The same ANCA can stimulate neutrophils to release NETs that include autoantigens and cause AAV patients to produce autoimmune responses to these components (29). At the same time, lymphocytopenia is considered to be related to inflammation burden, such as in rheumatoid arthritis, Crohn's disease, systemic lupus erythematosus, and vasculitis (30)(31)(32)(33). However, some studies found that lymphocytes are negatively correlated with the recurrence rate, with lymphocytopenia associated with a lower recurrence rate (34).…”

Pandemic influenza A (H1N1) virus causes abortive infection of primary human T cells

“…Accordingly, the potential mechanism of influenza and SARS-CoV induced lymphopenia could be distinguished. Up to now, it has been presumed that lymphopenia detected in cases of respiratory virus diseases might be due to inhibition of thymus for T-cell generation, abnormal cell death, tissue sequestration of lymphocytes, exhaustion, migration or homing from blood [ 34 , 35 ]. In particular, lymphopenia of severe influenza but not SARS patients could be a consequence of a direct infection in T cells and infection-induced apoptosis.…”

Symbiotic bacteria-dependent expansion of MR1-reactive T cells causes autoimmunity in the absence of Bcl11b

“…A link between lymphopenia and autoimmunity has been reported 51 . Under lymphopenic conditions, the compensatory expansion of T cells exhibiting innate T cell/T FH cell profiles, converts these cells into pathogenic effectors [52][53][54] .…”