Omenn syndrome: When T cells lose control
Omenn syndrome (OS) is an inherited disorder caused by hypomorphic mutations in recombination-activating genes (RAG) and characterized by the peculiar coexistence of severe combined immunodeficiency and autoimmunity. A lack of central tolerance contributes to the autoimmune pathology of the disease, leading to release of autoreactive T cells in the periphery. At this level, self-tolerance is enforced by CD4⁺CD25^high forkhead box protein 3 (FOXP3)–positive regulatory T cells. Cassani et al (p 209) analyze FOXP3 expression in the peripheral blood and lymphoid organs of 9 patients with OS. Although children with OS have a variable number of circulating FOXP3⁺ T lymphocytes, these cells coexpress activation markers, and when sorted on the basis of the CD4⁺CD25^hiCD127^low/- phenotype, they do not suppress proliferation of allogeneic activated CD4⁺CD25^- T cells. Furthermore, the authors report a severe reduction of FOXP3⁺ cells in lymph nodes and the thymus (see Figure) of patients with OS. These results indicate that expression of FOXP3 in peripheral blood of patients is not a reliable marker for regulatory T cells but rather is consistent with an in vivo T-cell activation process. Clinical applications of this research include the identification of previously unrecognized targets for therapeutic intervention while preparing for hematopoietic stem cell transplantation. Read the full article here.

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