Preventing SP cells from entering or accumulating in the medulla such as that in Ccr7-/- and plt mice, or defects in the medulla such as those caused by Aire and Relb deficiency could result in autoimmunity, strongly supporting the important role of the medullary microenvironment in SP thymocyte development, in particular, negative selection against self-reactivity [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36]. This evidence concerns the gene AIRE and Autoimmunity.