CD4 and allergic disease: The nTregs, defined as CD4+CD25+Foxp3+ cells, are generated in the thymus during the maturation of T-cells by recognition of self-peptides with intermediate affinity, whereas the iTregs are produced in secondary lymphoid organs (spleen and lymph nodes) from naïve CD4+Foxp3- T-cells under both homeostatic conditions and in the presence of inflammation, infection or allergy after stimulation with TGF-β (Piccioni et al., 2014).