Human interleukin-2 receptor α deficiency

Profound cellular immunodeficiency occurs because of mutations in proteins involved in the differentiation and function of mature lymphoid cells. This article describes a novel human immune aberration arising from a truncation mutation of the IL-2 receptor alpha (IL-2R alpha) chain (CD25), a subunit of the tripartite high-affinity receptor for IL-2. Decreased numbers of peripheral T cells displaying abnormal proliferation but normal B-cell development characterize this immunodeficiency. Extensive lymphocytic infiltration of tissues, including lung, liver, gut, and bone, is observed, accompanied by tissue atrophy and inflammation. Although mature T cells are present, the absence of CD25 does affect the differentiation of thymocytes. While displaying normal development of CD2, CD3, CD4, and CD8 expression, CD25-deficient cortical thymocytes do not express CD1; they fail to down-regulate levels of bcl-2 and, subsequently, apoptosis in the thymus is reduced markedly.