Portal de Periódicos da CAPES

A Broad Range of Self-Reactivity Drives Thymic Regulatory T Cell Selection to Limit Responses to Self

2012; Cell Press; Volume: 37; Issue: 3 Linguagem: Inglês

10.1016/j.immuni.2012.07.009

1097-4180

Hyang‐Mi Lee, Jhoanne L. Bautista, James Scott‐Browne, James F. Mohan, Chyi‐Song Hsieh,

Dermatology and Skin Diseases

The degree of T cell self-reactivity considered dangerous by the immune system, thereby requiring thymic selection processes to prevent autoimmunity, is unknown. Here, we analyzed a panel of T cell receptors (TCRs) with a broad range of reactivity to ovalbumin (OVA323-339) in the rat insulin promoter (RIP)-mOVA self-antigen model for their ability to trigger thymic self-tolerance mechanisms. Thymic regulatory T (Treg) cell generation in vivo was directly correlated with in vitro TCR reactivity to OVA-peptide in a broad ∼1,000-fold range. Interestingly, higher TCR affinity was associated with a larger Treg cell developmental “niche” size, even though the amount of antigen should remain constant. The TCR-reactivity threshold to elicit thymic negative selection and peripheral T cell responses was ∼100-fold higher than that of Treg cell differentiation. Thus, these data suggest that the broad range of self-reactivity that elicits thymic Treg cell generation is tuned to secure peripheral tolerance to self.