n engl j med 354;11 www.nejm.org march 16, 2006
The new england
journal of medicine
established in 1812
march 16, 2006
vol. 354 no. 11
CD4+ Invariant T-Cell–Receptor+ Natural Killer T Cells
in Bronchial Asthma
Omid Akbari, Ph.D., John L. Faul, M.D., Elisabeth G. Hoyte, M.S.N., Gerald J. Berry, M.D., Jan Wahlström, M.D., Ph.D.,
Mitchell Kronenberg, Ph.D., Rosemarie H. DeKruyff, Ph.D., and Dale T. Umetsu, M.D., Ph.D.
From the Division of Immunology, Chil-
dren’s Hospital Boston, and the Depart-
ment of Pediatrics, Harvard Medical
School — both in Boston (O.A., R.H.D.,
D.T.U.); the Division of Pulmonary and
Critical Care, Department of Medicine
( J.L.F.), the Department of Pediatrics
(E.G.H., D.T.U.), and the Department of
Pathology (G.J.B.), Stanford University,
Stanford, Calif.; the Division of Respirato-
ry Medicine and Department of Medicine,
Karolinska Institute, Stockholm (J.W.);
and the Division of Developmental Im-
munology, La Jolla Institute for Allergy
and Immunology, San Diego, Calif. (M.K.).
Address reprint requests to Dr. Umetsu
at the Division of Immunology, Children’s
Hospital Boston, Harvard Medical School,
Karp Research Laboratories, 1 Blackfan
Cir., Rm. 10127, Boston, MA 02115, or at
Drs. Akbari and Faul contributed equally
to this article.
N Engl J Med 2006;354:1117-29.
Copyright © 2006 Massachusetts Medical Society.
Bronchial asthma is associated with an inflammatory process that is characterized
by the presence in the airways of large numbers of CD4+ T cells producing inter-
leukin-4 and interleukin-13. However, the CD4 antigen is expressed not only by
class II major histocompatibility complex (MHC)–restricted CD4+ T cells, but also
by a newly identified subgroup of T cells, CD1d-restricted natural killer T cells.
These cells express a conserved (invariant) T-cell receptor and have a potent im-
munoregulatory function. Because mouse models of allergic asthma indicate that
natural killer T cells are required