Tolerance has its limits: how the thymus copes with infection

The thymus is required for T cell differentiation; a process that depends on which antigens are encountered by thymocytes, the environment surrounding the differentiating cells, and the thymic architecture. These features are altered by local infection of the thymus and by the inflammatory mediators that accompany systemic infection. Although once believed to be an immune privileged site, it is now known that antimicrobial responses are recruited to the thymus. Resolving infection in the thymus is important because chronic persistence of microbes impairs the differentiation of pathogen-specific T cells and diminishes resistance to infection. Understanding how these mechanisms contribute to disease susceptibility, particularly in infants with developing T cell repertoires, requires further investigation.We thank Joana Neves and Nadine Santos for critical reading of the manuscript. This work was supported by Portuguese Foundation for Science and Technology (FCT) grant PTDC/SAU-MII/101663/2008 and individual fellowships to CN-A and CN. SMB was supported by National Institutes of Health Grant R01 R56 AI067731