Editors' ChoiceImmunology

Beware of T Cells That Don't Know How to Stop

Sci. Signal.  30 Sep 2014:
Vol. 7, Issue 345, pp. ec269
DOI: 10.1126/scisignal.2005955

During an infection, T cells divide extensively and secrete proteins that can severely damage tissues. But T cells know when to stop—they express proteins on their surface, such as CTLA4, which put on the brakes. Kuehn et al. now report genetic evidence of the importance of CTLA4 in humans (see the Perspective by Rieux-Laucat and Casanova). They identified six patients with mutations in one copy of CTLA4. Patients presented with symptoms of an overzealous immune response, with immune cells infiltrating their organs. The findings support the idea that CTLA4 tells the immune system when enough is enough.

H. S. Kuehn, W. Ouyang, B. Lo, E. K. Deenick, J. E. Niemela, D. T. Avery, J.-N. Schickel, D. Q. Tran, J. Stoddard, Y. Zhang, D. M. Frucht, B. Dumitriu, P. Scheinberg, L. R. Folio, C. A. Frein, S. Price, C. Koh, T. Heller, C. M. Seroogy, A. Huttenlocher, V. K. Rao, H. C. Su, D. Kleiner, L. D. Notarangelo, Y. Rampertaap, K. N. Olivier, J. McElwee, J. Hughes, S. Pittaluga, J. B. Oliveira, E. Meffre, T. A. Fleisher, S. M. Holland, M. J. Lenardo, S. G. Tangye, G. Uzel, Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. Science 345, 1623–1627 (2014). [Abstract] [Full Text]

F. Rieux-Laucat, J.-L. Casanova, Autoimmunity by haploinsufficiency. Science 345, 1560–1561 (2014). [Abstract] [Full Text]