title: Oligoclonal expansion of CD45RO+ T lymphocytes in Omenn syndrome.
abstract: Omenn syndrome comprises a rare form of combined immunodeficiency with TH2-type features of eosinophilia and elevated IgE. Previous studies have led to reports of restricted heterogeneity in the T lymphocyte repertoire, and in vitro cloned T lymphocytes have been shown to produce IL-4 and IL-5. We hypothesized that (1) T cell receptor beta V(D)J DNA sequence analysis would confirm and further define the putative restricted heterogeneity, and (2) increased production of IL-4 and IL-5 should be found in nonstimulated T lymphocytes, if the molecular pathogenesis of Omenn syndrome is an uncontrolled TH2 state. We report the results of molecular analyses of T lymphocytes from an untreated 3-month-old patient. Oligoclonal T cell receptor beta variable gene usage was found. Sequence analysis revealed sets of identical V(D)J sequences, each in-frame, with apparently normal N-diversification and no obvious antigen combining site motif. From fresh, nonstimulated lymphocytes, proinflammatory TH1 cytokines could be detected, but TH2 cytokines could not, so that a simple TH1/TH2 paradigm cannot explain the eosinophilia and elevated IgE in Omenn syndrome. Our studies fully document for the first time at the molecular level that clonally expanded populations of T lymphocytes are present in Omenn syndrome.
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: T O
authors.initials: TO
authors.lastname: Harville
authors.forename: D M
authors.initials: DM
authors.lastname: Adams
authors.forename: T A
authors.initials: TA
authors.lastname: Howard
authors.forename: R E
authors.initials: RE
authors.lastname: Ware
mesh_terms: D000596:Amino Acids / Q000235:genetics; D002999:Clone Cells; D016207:Cytokines / Q000235:genetics; D003873:Dermatitis, Exfoliative / Q000276:immunology; D004802:Eosinophilia / Q000276:immunology; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D007231:Infant, Newborn; D017493:Leukocyte Common Antigens / Q000032:analysis*; D008218:Lymphocytosis / Q000276:immunology; D008297:Male; D005810:Multigene Family / Q000276:immunology; D014176:Protein Biosynthesis / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000276:immunology*; D013577:Syndrome; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
chemical_list: D000596:Amino Acids; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007073:Immunoglobulin E; D017493:Leukocyte Common Antigens