Abstract
CD4+ follicular helper T (Tfh) cells constitute a subset of effector T cells that participate in the generation of high-affinity humoral responses. They express the chemokine receptor CXCR5 and produce the cytokine IL-21, both of which are required for their contribution to germinal center formation. Uncontrolled expansion of Tfh cells is observed in various mouse models of systemic autoimmune diseases and in patients with these diseases. In particular, the frequency of circulating Tfh is correlated with disease activity and anti-DNA antibody titer in patients with systemic lupus erythematosus. Recent studies reveal functional diversity within the Tfh population in both humans and mice. We will summarize here the molecular mechanisms for Tfh cell generation, survival and function in both humans and mice, and the relationship between Tfh cells and autoimmune disease in animal models and in patients.
Highlights
It has long been known that T cells are required for successful humoral immune responses [1]
CXCR5loBCL6lo pre-Tfh cells interact with cognate B cells at the T–B zone to induce a high level of B cell lymphoma 6 (BCL6) and CXCR5
This study suggests that the number of Tfh cells, and the antigenic specificity of Tfh cells is likely essential to immune tolerance
Summary
The Feinstein Institute for Medical Research, Northwell Health, New York, NY, United States. CD4+ follicular helper T (Tfh) cells constitute a subset of effector T cells that participate in the generation of high-affinity humoral responses. They express the chemokine receptor CXCR5 and produce the cytokine IL-21, both of which are required for their contribution to germinal center formation. We will summarize here the molecular mechanisms for Tfh cell generation, survival and function in both humans and mice, and the relationship between Tfh cells and autoimmune disease in animal models and in patients. Reviewed by: Koji Yasutomo, Tokushima University, Japan Lewis Zhichang Shi, Case Western Reserve University, United States. Follicular Helper T Cells in Systemic Lupus Erythematosus
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