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. Author manuscript; available in PMC: 2012 Jan 1.
Published in final edited form as: Trends Immunol. 2010 Nov 23;32(1):26–33. doi: 10.1016/j.it.2010.10.005

Figure 3. A “Hit and Run” model for thymic Treg cell differentiation.

Figure 3

Thymocytes receiving low-affinity antigen stimulation are positively selected, and develop into conventional T cells. T cells do not express Foxp3 in the absence of nuclear NF-κB. Thymocytes receiving continuous high-affinity antigen stimulation are deleted by negative selection. T cells fail to express Foxp3 due to the inactivation of Foxo proteins. Thymocytes with infrequent encounters with high-affinity antigens develop into natural Treg cells. High-affinity antigen stimulation in the presence of B7-activated CD28 signals activates NF-κB via IKK, and inactivates Foxo proteins via Akt. Upon the cessation of antigen stimulation, Foxo proteins translocate back to the nucleus, and cooperate with NF-κB to induce Foxp3 gene transcription. Signals from the common γ-chain cytokine IL-2 may also regulate Foxp3 expression.