Fig. 1: The development of regulatory T cells.
Regulatory T cells (Tregs) in the thymus derive from CD4+ single positive T cells when the TCR signal is strong, and IL-2 + Transforming Growth Factor Beta (TGFβ) is supplemented. These Tregs are naïve to foreign antigen and therefore display a CD45RA+ phenotype. Upon antigen encounter, Tregs upregulate FOXP3 and CD45RO expression and are termed effector Tregs. In the periphery, a naïve CD4+T cell can become an Induced Treg or an activated T cell depending on the three signals received by an antigen-presenting cell. These three signals include (1) antigen presentation via MHC, (2) co-stimulation through B7.1/B7.2 and (3) cytokine signaling. CD4+ activated T cells can differentiate into an induced Treg based on the cytokine signal received in the microenvironment. Markers to distinguish Tregs based on development stage are listed in the box beside the cell. IL interleukin, SP single positive, CD cluster of differentiation, FOXP3 forkhead box P3, TCR T-cell receptor, HLA human leukocyte antigen, MHC major histocompatibility complex, B7.1/B7.2 CD80 and CD86. Figure was adapted from Sakaguchi et al. and Josefowicz et al.2,147 and created in BioRender. Pacheco, A. (2026) https://BioRender.com/012h2r5.
