TY - JOUR AU - Taco W. Kuijpers, AU - Ester M.M. van Leeuwen, AU - Barbara H. Barendregt, AU - Paul Klarenbeek, AU - Daan J. aan de Kerk, AU - Paul A. Baars, AU - Machiel H. Jansen, AU - Niek de Vries, AU - René A.W. van Lier, AU - Mirjam van der Burg, PY - 2013/06/30 Y2 - 2024/03/28 TI - A reversion of an IL2RG mutation in combined immunodeficiency providing competitive advantage to the majority of CD8+ T cells JF - Haematologica JA - haematol VL - 98 IS - 7 SE - Original Articles and Brief Reports DO - 10.3324/haematol.2012.077511 UR - https://haematologica.org/article/view/6711 SP - 1030-1038 AB - Mutations in the common gamma chain (γc, CD132, encoded by the IL2RG gene) can lead to B+T−NK− X-linked severe combined immunodeficiency, as a consequence of unresponsiveness to γc-cytokines such as interleukins-2, -7 and -15. Hypomorphic mutations in CD132 may cause combined immunodeficiencies with a variety of clinical presentations. We analyzed peripheral blood mononuclear cells of a 6-year-old boy with normal lymphocyte counts, who suffered from recurrent pneumonia and disseminated mollusca contagiosa. Since proliferative responses of T cells and NK cells to γc -cytokines were severely impaired, we performed IL2RG gene analysis, showing a heterozygous mutation in the presence of a single X-chromosome. Interestingly, an IL2RG reversion to normal predominated in both naïve and antigen-primed CD8+ T cells and increased over time. Only the revertant CD8+ T cells showed normal expression of CD132 and the various CD8+ T cell populations had a different T-cell receptor repertoire. Finally, a fraction of γδ+ T cells and differentiated CD4+CD27− effector-memory T cells carried the reversion, whereas NK or B cells were repeatedly negative. In conclusion, in a patient with a novel IL2RG mutation, gene-reverted CD8+ T cells accumulated over time. Our data indicate that selective outgrowth of particular T-cell subsets may occur following reversion at the level of committed T progenitor cells. ER -