Impaired T-cell receptor activation in IL-1 receptor-associated kinase-4-deficient patients.
BACKGROUND
IL-1 receptor-associated kinase 4 (IRAK-4) is an effector of the Toll-like receptor and IL-1 receptor pathways that plays a critical role in innate immune responses. The role of IRAK-4 in adaptive immune functions in human subjects is incompletely understood.


OBJECTIVE
We sought to evaluate T-cell function in IRAK-4 deficient patients.


METHODS
We compared upregulation of CD25 and CD69 on T cells and production of IL-2, IL-6, and IFN-gamma after stimulation of PBMCs from 4 IRAK-4-deficient patients and healthy control subjects with anti-CD3 and anti-CD28.


RESULTS
Upregulation of CD25 and CD69 on T cells and production of IL-6 and IFN-gamma, but not IL-2, was significantly reduced in IRAK-4-deficient patients.


CONCLUSIONS
IRAK-4-deficient patients have defects in T-cell activation.
McDonald
Douglas R
DR
Division of Immunology, Children's Hospital, Boston, and the Department of Pediatrics, Harvard Medical School, Boston, Mass, USA.
Goldman
Frederick
F
Gomez-Duarte
Oscar D
OD
Issekutz
Andrew C
AC
Kumararatne
Dinakantha S
DS
Doffinger
Rainer
R
Geha
Raif S
RS
D056704:Adaptive Immunity / Q000235:genetics / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D005260:Female; D030342:Genetic Diseases, Inborn / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D053592:Interleukin-1 Receptor-Associated Kinases; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D011948:Receptors, Antigen, T-Cell; D000099192:CD69 Antigens; C508017:IL2RA protein, human; C507773:IRAK4 protein, human