Beyond Regulatory T Cells: The Potential Role for IL-2 to Deplete T-Follicular Helper Cells and Treat Autoimmune Diseases

Abstract

Low-dose IL-2 administration suppresses unwanted immune responses in mice and humans, thus evidencing the potential of IL-2 to treat autoimmune disorders. Increased Tregs activity is one of the potential mechanisms by which low-dose IL-2 immunotherapy induces immunosuppression. In addition, recent data indicate that IL-2 may contribute to prevent unwanted self-reactive responses by preventing the developing of T-follicular helper cells, a CD4+ T-cell subset that expands in autoimmune disease patients and promotes long-term effector B-cell responses. Here we discuss the mechanisms underlying the clinical benefits of low-dose IL-2 administration, focusing on the role of this cytokine in promoting Treg-mediated suppression and preventing self-reactive T-follicular helper cell responses.

Kronik Hepatit B ve C Enfeksiyonu ile Interlokin-2 (-330) Gen Polimorfizmi Arasindaki Iliskinin Arastirilmasi

“…IL-2Rα bağlanmada düşük affiniteye sahipken, β ve γ IL-2R affinitesini 100 kat artırma yeteneğinde olup, bu ikisi T hücrelerde sinyal oluşumu için gereklidir. IL-2, primer olarak aktive edilmiş CD4 T hücreler tarafından oluşturulmakla birlikte, CD8 T hücreler (TH0,TH1), dendiritik hücreler ve timik hücreler tarafından da ifade edildiği gösterilmiştir (7)(8)(9)(10)(11). Ayrıca transformasyona uğramış T-hücreler, B-hücreler, lösemi hücreleri, LAK hücreler (lymphokineactivated killer cells) ve NK (natural killer: doğal öldürücü) hücrelerde IL-2 salgılamaktadırlar (12).…”

“…IL-2, düzenleyici T hücrelerin (Treg) homeostasizinde de önemli rol oynamakta, T hücrelerinin ve diğer yanıtların düzenlenmesi ve baskılanmasında rolü olan Treg hücrelerin fonksiyonlarını tamamlamaları ve yaşamlarını sürdürmeleri için gerekli olmaktadır (9,10,13). Farelerde yapılan bir çalışmada IL-2 yokluğunun akut hastalıkların daha az ciddi seyretmesine neden olduğu, buna karşın kronik progresif hastalıkların gelişmesine yol açtığı gösterilmiştir (14).…”

Mapping the effects of vitamin D in multiple sclerosis

“…Integration of CD25 in the intermediate-affinity IL-2R heterodimer, consisting of IL-2Rβ (CD122) and the common γ-chain (CD132), renders a high-affinity IL-2R [68] . This high-affinity IL-2R complex is expressed on activated T cells and, therefore, the IL-2/IL-2R pathway is considered essential in T cell proliferation and survival [68][69][70][71][72] . This is underlined by the introduction of therapies that target CD25 in order to block expansion of pathogenic T cells in transplantation and autoimmune diseases [73] .…”

“…The gradual reduction of CD25 cell surface expression in particularly Treg, and an attenuation hereof by vitamin D supplements, could be relevant for the disease process of MS. After all, IL-2 signaling is important for Treg survival [68][69][70][71][72] . Moreover, CD25 may be (indirectly) important for Treg function: in CD25-deficient mice Treg were lacking not only expression of CD25, but also FoxP3 [98] , which is considered mandatory for the immune suppressive function [99] .…”

“…Whether the associations between vitamin D and MS activity at MS onset are driven by a disease modulating effect of vitamin D on MS T cell pathway-related genes have been associated with multiple sclerosis (MS), including the gene encoding for the α-chain of the interleukin-2 receptor complex (IL-2Rα or CD25) [32] . Integration of CD25 in the intermediate-affinity IL-2R heterodimer, consisting of IL-2Rβ (CD122) and the common γ-chain (CD132), renders a high-affinity IL-2R [68] . This high-affinity IL-2R complex is expressed on activated T cells and, therefore, the IL-2/IL-2R pathway is considered essential in T cell proliferation and survival [68][69][70][71][72] .…”