title: Engrafted maternal T cells in a severe combined immunodeficiency patient express T-cell receptor variable beta segments characterized by a restricted V-D-J junctional diversity.
abstract: To better understand the peculiar functional behavior of engrafted maternal T cells in a severe combined immunodeficiency (SCID) patient, we characterized, at the molecular level, the T-cell repertoire of a SCID child with a high number of engrafted, mature, activated lymphocytes. We found that, although these transplacentally acquired T cells express a random set of T-cell receptor variable beta (TCRBV) segments, the TCRBV transcripts are characterized by an extremely restricted V-D-J junctional diversity. Only a few cDNA clones were dominant among the TCRBV4+, TCRBV6+, and TCRBV20+ populations in engrafted cells, whereas the same TCRBV chains expressed by the mother's lymphocytes had the expected junctional hetero-geneity. Highly diverse and polyclonal junctions were also expressed by maternal cells activated in mixed lymphocyte reaction by Epstein-Barr virus (EBV)-transformed B lymphocytes from the patient, indicating that the strong clonal selection that characterizes the engrafted cells repertoire is probably not due to allorecognition. Furthermore, we report that the repertoire of the transplacentally acquired lymphocytes is dynamic over time and is characterized by waves of expression and contraction of selected clones, expressing different TCRBV segments. These results help to explain some of the abnormal functional behaviors of engrafted maternal cells and raise new questions regarding the mechanisms responsible for the restricted clonal diversity.
authors.affiliation: Consorzio per le Biotecnologie, Terzo Laboratorio Analisi, Servizio di Immunologia Clinica, Spedali Civili, Brescia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Sottini
authors.forename: E
authors.initials: E
authors.lastname: Quiròs-Roldan
authors.forename: L D
authors.initials: LD
authors.lastname: Notarangelo
authors.forename: A
authors.initials: A
authors.lastname: Malagoli
authors.forename: D
authors.initials: D
authors.lastname: Primi
authors.forename: L
authors.initials: L
authors.lastname: Imberti
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D016026:Bone Marrow Transplantation; D002678:Chimera; D002999:Clone Cells; D005260:Female; D005786:Gene Expression Regulation; D006085:Graft Survival; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007112:Immunity, Maternally-Acquired; D016130:Immunophenotyping; D007223:Infant; D008213:Lymphocyte Activation; D008297:Male; D008431:Maternal-Fetal Exchange; D018448:Models, Immunological; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016511:Severe Combined Immunodeficiency / Q000196:embryology / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes; D013997:Time Factors
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens