Abstract

The molecular mechanisms directing the development of 'natural' CD4⁺CD25⁺Foxp3⁺ regulatory T cells (T_reg cells) in the thymus are not thoroughly understood. We show here that conditional deletion of transforming growth factor- receptor I (TRI) in T cells blocked the appearance of CD4⁺CD25⁺Foxp3⁺ thymocytes at postnatal days 3–5. Paradoxically, however, beginning 1 week after birth, the same TRI-mutant mice showed accelerated expansion of thymic CD4⁺CD25⁺Foxp3⁺ populations. This rapid recovery of Foxp3⁺ thymocytes was attributable mainly to overproduction of and heightened responsiveness to interleukin 2, as genetic ablation of interleukin 2 in TRI-mutant mice resulted in a complete absence of CD4⁺CD25⁺Foxp3⁺ cells from the thymus and periphery. Thus, transforming growth factor- signaling is critical to the thymic development of natural CD4⁺CD25⁺Foxp3⁺ T_reg cells.

1. Mucosal Immunology Unit, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
2. Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.

Correspondence to: WanJun Chen¹ e-mail: wchen@mail.nih.gov

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