"Dystrophy" - A Mechanism How Tregs Lead Effector T cells to Apoptosis

CD4+ CD25+ Foxp3+ regulatory T cells (Tregs) have been well known to regulate immune responses, including suppress effector CD4+ T cells. However, the molecular mechanisms underlie this process is in debate. Pandiyan P. et al. revealed an inetersting perspective on Nature Immunology, which I interpret it as "dystrophy".

First, the authors reconfirmed that Treg cells induce effector T cells apoptosis, in a time-dependent manner, by in vitro assay with coculuture of Tregs and effector T cells.

Further, they showed that additions of cytokines that signal through the common gamma chain, will rescue, though in different degree, this apoptosis effect. Among these the IL-2 (Interleukin 2) has the greatest effect. On the other hand, the authors uncovered that the supernatant of Tregs cocultured with effector Tcells has much less IL-2 concentration than control. They further proved that it was due to Tregs imbibed far more IL-2 than than naive control T cell did, whereas IL-2 expression by effector T cells remained constant at mRNA and protein level in both circumstances.

Before the effector T cells are killed, they had less expression of cytokine receptors CD25 and CD132, indicating impaired positive feedback loop by IL-2.

Meanwhile, the authors also revealed that Bim-deficient effector T cells were completely protected from apoptosis caused by Tregs. Overexpressing Bcl-2 also protected them. These echoes the findings that Bcl-2 inhibit cytokine deprivation-induced apoptosis, and Bim promotes it.

Using scid mice modeled for inflammatory bowel disease, the authors provided more evidences of apoptosis associated with Tregs, although I didn't see they further clarify the point of cytokine deprivation-mediated apoptosis by this approach.

In conclusion, this is an intriguing paper broaching a concept of "nutrition and malnutrition" in cellular level. Short in IL-2, the dystrophic effector T cells finally go apoptosis, which maintain the immune system in a balanced and homeostatic status.
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Tags: Dystrophy, Regulatory T cell, Treg, Effector T cell, Apoptosis, Survival, CD4+CD25+Foxp3+ Treg, CD4+ T cells, cytokine, common gamma chain, Interleukin, IL-2, IL-2 receptor, cytokine receptor, CD25, CD132, mRNA expression, protein, Bcl-2 family, Bim, Bcl-2, scid mice, IBD, inflammatory bowel disease, nutrition, malnutrition, immune system, autoimmune disease, Medicine-Immunology, Medicine-Molecular Biology, Medicine-Gastroenterology, Medicine-Rheumatology