Cutting edge: Thymic selection and autoreactivity are regulated by multiple coreceptors involved in T cell activation

Immune responses are shaped by several processes that promote responses to pathogens and hinder responses to self. One mechanism that contributes to t his polarization in response is negative selection, in which thymocytes tha t can respond to self-peptide/MHC complexes are deleted from the T cell rep ertoire. I found here that several coreceptors known to contribute to matur e T cell activation also participate in negative selection. Interestingly, these molecules appeared to act in a cooperative fashion. Blocking the cont ribution of these molecules in fetal thymus organ culture not only prevente d negative selection in the CD4(+) lineage, but also induced the appearance of autoreactive thymocytes. This is the first demonstration that blocking coreceptor interactions during thymic development can produce autoreactive T cells. The contribution of negative selection to the mature T cell repert oire and to autoimmunity is discussed in light of these results.