Peripheral tolerance keeps our immune system from attacking our own tissues, and regulatory T cells are its key enforcers—with FOXP3 as their master switch. When FOXP3 is mutated, you see devastating autoimmunity, proving Tregs aren't just bystanders but essential. Anergy in conventional T cells is another layer, a functional silencing.
In my Bangalore lab, watching Tregs from inflamed joints fail to suppress, despite expressing FOXP3, tells me the local microenvironment can override even this central regulator. The textbook hierarchy isn't absolute.
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