Nature Immunology
4, 261 - 268 (2003)
Published online: 10 February 2003; | doi:10.1038/ni902
Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiencyBodo Grimbacher1, 5, Andreas Hutloff2, 5, Michael Schlesier1, Erik Glocker1, Klaus Warnatz1, Ruth Dräger1, Hermann Eibel3, Beate Fischer3, Alejandro A. Schäffer4, Hans W. Mages2, Richard A. Kroczek2, 5
& Hans H. Peter1, 51
Division of Rheumatology and Clinical Immunology, Medical School, University of Freiburg, Hugstetterstr. 55, 79106 Freiburg, Germany. 2
Molecular Immunology, Robert Koch-Institute, Nordufer 20, 13353 Berlin, Germany. 3
Clinical Research Unit for Rheumatology, University Hospital Freiburg, Breisacherstr. 64, 79106 Freiburg, Germany. 4
National Center for Biotechnology Information, National Institutes of Health, Department of Health and Human Services, 8600 Rockville Pike, Bethesda, Maryland 20894, USA. 5
These authors contributed equally to this work.
Correspondence should be addressed to Hans H. Peter peterhh@medizin.ukl.uni-freiburg.deNo genetic defect is known to cause common variable immunodeficiency (CVID), a heterogeneous human disorder leading to adult-onset panhypogammaglobulinemia. In a search for CVID candidate proteins, we found four of 32 patients to lack ICOS, the "inducible costimulator" on activated T cells, due to an inherited homozygous deletion in the ICOS gene. T cells from these individuals were normal with regard to subset distribution, activation, cytokine production and proliferation. In contrast, naive, switched and memory B cells were reduced. The phenotype of human ICOS deficiency, which differs in key aspects from that of the ICOS-/- mouse, suggests a critical involvement of ICOS in T cell help for late B cell differentiation, class-switching and memory B cell generation.
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