T Cell Receptor Repertoire and Function in Patients with DiGeorge Syndrome and Velocardiofacial Syndrome

Overview

Journal Clin Exp Immunol

Publisher Oxford University Press

Specialty Allergy & Immunology

Date 2000 Jul 11

PMID 10886249

Citations 12

Authors

M Pierdominici

M Marziali

A Giovannetti

A Oliva

R Rosso

B Marino

M C Digilio

A Giannotti

G Novelli

B Dallapiccola

F Aiuti

F Pandolfi

Affiliations

Soon will be listed here.

Abstract

DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS) are associated with chromosome 22q11.2 deletion. Limited information is available on the T cell receptor (TCR) Vbeta repertoire. We therefore investigated TCR Vbeta families in lymphocytes isolated from blood and thymic samples of seven patients with DGS and seven patients with VCFS, all with 22q11.2 deletion. We also studied activities related to TCR signalling including in vitro proliferation, anti-CD3-induced protein tyrosine phosphorylation, and susceptibility to apoptosis. Reduced CD3+ T cells were observed in most patients. Spontaneous improvement of T cell numbers was detected in patients, 3 years after the first study. Analysis of CD4+ and CD8+ TCR Vbeta repertoire in peripheral and thymic cells showed a normal distribution of populations even if occasional deletions were observed. Lymphoproliferative responses to mitogens were comparable to controls as well as anti-CD3-induced protein tyrosine phosphorylation. Increased anti-CD3-mediated apoptosis was observed in thymic cells. Our data support the idea that in patients surviving the correction of cardiac anomalies, the immune defect appears milder than originally thought, suggesting development of a normal repertoire of mature T cells.

Citing Articles

Review of the Pathophysiology and Clinical Manifestations of 22q11.2 Deletion and Duplication Syndromes.

Purow J, Waidner L, Ale H Clin Rev Allergy Immunol. 2025; 68(1):23.

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Editorial to the Special Issue "Clinical Immunology in Italy, with Special Emphasis to Primary and Acquired Immunodeficiencies: A Commemorative Issue in Honor of Prof. Fernando Aiuti".

Aiuti A, DAmelio R, Quinti I, Rossi P Biomedicines. 2023; 11(12).

PMID: 38137412 PMC: 10741147. DOI: 10.3390/biomedicines11123191.

Clinical Practice Guidelines for the Immunological Management of Chromosome 22q11.2 Deletion Syndrome and Other Defects in Thymic Development.

Mustillo P, Sullivan K, Chinn I, Notarangelo L, Haddad E, Davies E J Clin Immunol. 2023; 43(2):247-270.

PMID: 36648576 PMC: 9892161. DOI: 10.1007/s10875-022-01418-y.

COVID-19 Severity, Cardiological Outcome, and Immunogenicity of mRNA Vaccine on Adult Patients With 22q11.2 DS.

Pulvirenti F, Piano Mortari E, Putotto C, Terreri S, Salinas A, Cinicola B J Allergy Clin Immunol Pract. 2022; 11(1):292-305.e2.

PMID: 36280136 PMC: 9584833. DOI: 10.1016/j.jaip.2022.10.010.

Lymphocyte Apoptosis and FAS Expression in Patients with 22q11.2 Deletion Syndrome.

Aresvik D, Overland T, Lima K, Pettersen R, Abrahamsen T J Clin Immunol. 2018; 39(1):65-74.

PMID: 30569262 DOI: 10.1007/s10875-018-0579-7.

References

KERR J, Wyllie A, Currie A . Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972; 26(4):239-57. PMC: 2008650. DOI: 10.1038/bjc.1972.33. View

Markert M, Boeck A, Hale L, Kloster A, McLaughlin T, Batchvarova M . Transplantation of thymus tissue in complete DiGeorge syndrome. N Engl J Med. 1999; 341(16):1180-9. DOI: 10.1056/NEJM199910143411603. View

Radford D, Perkins L, Lachman R, Thong Y . Spectrum of Di George syndrome in patients with truncus arteriosus: expanded Di George syndrome. Pediatr Cardiol. 1988; 9(2):95-101. DOI: 10.1007/BF02083707. View

Slade H, GREENWOOD J, Beekman 3rd R, McCoy Jr J, Hudson J, Pahwa S . Flow cytometric analysis of lymphocyte subpopulations in infants with congenital heart disease. J Clin Lab Anal. 1989; 3(1):14-20. DOI: 10.1002/jcla.1860030105. View

Bastian J, Law S, Vogler L, Lawton A, Herrod H, Anderson S . Prediction of persistent immunodeficiency in the DiGeorge anomaly. J Pediatr. 1989; 115(3):391-6. DOI: 10.1016/s0022-3476(89)80837-6. View

McConkey D, Hartzell P, Orrenius S, Jondal M . Calcium-dependent killing of immature thymocytes by stimulation via the CD3/T cell receptor complex. J Immunol. 1989; 143(6):1801-6. View

Muller W, Peter H, Kallfelz H, Franz A, Rieger C . The DiGeorge sequence. II. Immunologic findings in partial and complete forms of the disorder. Eur J Pediatr. 1989; 149(2):96-103. DOI: 10.1007/BF01995856. View

Li Y, Szabo P, Robinson M, Dong B, Posnett D . Allelic variations in the human T cell receptor V beta 6.7 gene products. J Exp Med. 1990; 171(1):221-30. PMC: 2187675. DOI: 10.1084/jem.171.1.221. View

Pandolfi F, Foa R, DE Rossi G, Zambello R, Chisesi T, Di Celle P . Clonally expanded CD3+, CD4-, CD8- cells bearing the alpha/beta or the gamma/delta T-cell receptor in patients with the lymphoproliferative disease of granular lymphocytes. Clin Immunol Immunopathol. 1991; 60(3):371-83. DOI: 10.1016/0090-1229(91)90094-q. View

10.

Hong R . The DiGeorge anomaly. Immunodefic Rev. 1991; 3(1):1-14. View

11.

Driscoll D, Budarf M, Emanuel B . A genetic etiology for DiGeorge syndrome: consistent deletions and microdeletions of 22q11. Am J Hum Genet. 1992; 50(5):924-33. PMC: 1682598. View

12.

Hannet I, Erkeller-Yuksel F, Lydyard P, Deneys V, DeBruyere M . Developmental and maturational changes in human blood lymphocyte subpopulations. Immunol Today. 1992; 13(6):215, 218. DOI: 10.1016/0167-5699(92)90157-3. View

13.

Pandolfi F, Trentin L, San Martin J, Wong J, Kurnick J, Moscicki R . T cell heterogeneity in patients with common variable immunodeficiency as assessed by abnormalities of T cell subpopulations and T cell receptor gene analysis. Clin Exp Immunol. 1992; 89(2):198-203. PMC: 1554438. DOI: 10.1111/j.1365-2249.1992.tb06932.x. View

14.

Carey A, Kelly D, Halford S, Wadey R, Wilson D, Goodship J . Molecular genetic study of the frequency of monosomy 22q11 in DiGeorge syndrome. Am J Hum Genet. 1992; 51(5):964-70. PMC: 1682857. View

15.

Driscoll D, Spinner N, Budarf M, McDonald-McGinn D, Zackai E, Goldberg R . Deletions and microdeletions of 22q11.2 in velo-cardio-facial syndrome. Am J Med Genet. 1992; 44(2):261-8. DOI: 10.1002/ajmg.1320440237. View

16.

Kelly D, Goldberg R, Wilson D, Lindsay E, Carey A, Goodship J . Confirmation that the velo-cardio-facial syndrome is associated with haplo-insufficiency of genes at chromosome 22q11. Am J Med Genet. 1993; 45(3):308-12. DOI: 10.1002/ajmg.1320450306. View

17.

Goldberg R, Motzkin B, Marion R, Scambler P, Shprintzen R . Velo-cardio-facial syndrome: a review of 120 patients. Am J Med Genet. 1993; 45(3):313-9. DOI: 10.1002/ajmg.1320450307. View

18.

Pandolfi F, Oliva A, Sacco G, Polidori V, Liberatore D, Mezzaroma I . Fibroblast-derived factors preserve viability in vitro of mononuclear cells isolated from subjects with HIV-1 infection. AIDS. 1993; 7(3):323-9. DOI: 10.1097/00002030-199303000-00003. View

19.

Pannetier C, Cochet M, Darche S, Casrouge A, Zoller M, Kourilsky P . The sizes of the CDR3 hypervariable regions of the murine T-cell receptor beta chains vary as a function of the recombined germ-line segments. Proc Natl Acad Sci U S A. 1993; 90(9):4319-23. PMC: 46498. DOI: 10.1073/pnas.90.9.4319. View

20.

Driscoll D, Salvin J, Sellinger B, Budarf M, McDonald-McGinn D, Zackai E . Prevalence of 22q11 microdeletions in DiGeorge and velocardiofacial syndromes: implications for genetic counselling and prenatal diagnosis. J Med Genet. 1993; 30(10):813-7. PMC: 1016560. DOI: 10.1136/jmg.30.10.813. View