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. 1993 Mar;91(3):1214–1218. doi: 10.1172/JCI116282

Increased radiosensitivity of granulocyte macrophage colony-forming units and skin fibroblasts in human autosomal recessive severe combined immunodeficiency.

M Cavazzana-Calvo 1, F Le Deist 1, G De Saint Basile 1, D Papadopoulo 1, J P De Villartay 1, A Fischer 1
PMCID: PMC288079  PMID: 8450050

Abstract

We studied the radiosensitivity of granulocyte macrophage colony-forming units (GM-CFU) in patients with a severe combined immunodeficiency (SCID). Three patients lacking both mature T and B cells showed a twofold higher GM-CFU radiosensitivity calculated as the DO value (dose required to reduce survival to 37%), and an identical observation was made with fibroblasts from one of these patients. A patient with an SCID with hypereosinophilia, i.e., Omenn's syndrome characterized by extremely restricted T cell heterogeneity and a lack of B cells, also showed abnormal GM-CFU radiosensitivity. In contrast, GM-CFU from a patient lacking only T cells (X-linked form of SCID) showed normal GM-CFU radiosensitivity. These data further support the similarity between human T(-) B(-) SCID and the murine acid mutation characterized by a defect in T cell receptor and immunoglobulin gene rearrangement, and by an abnormal double-strand DNA break repair function. In addition, they strongly suggest that the Omenn's immunodeficiency syndrome may be a leaky T(-)B(-) SCID phenotype as previously indicated by the coexistence of the two phenotypes in siblings.

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Selected References

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  1. Arveiler B., de Saint-Basile G., Fischer A., Griscelli C., Mandel J. L. Germ-line mosaicism simulates genetic heterogeneity in Wiskott-Aldrich syndrome. Am J Hum Genet. 1990 May;46(5):906–911. [PMC free article] [PubMed] [Google Scholar]
  2. Bosma G. C., Custer R. P., Bosma M. J. A severe combined immunodeficiency mutation in the mouse. Nature. 1983 Feb 10;301(5900):527–530. doi: 10.1038/301527a0. [DOI] [PubMed] [Google Scholar]
  3. Bosma G. C., Davisson M. T., Ruetsch N. R., Sweet H. O., Shultz L. D., Bosma M. J. The mouse mutation severe combined immune deficiency (scid) is on chromosome 16. Immunogenetics. 1989;29(1):54–57. doi: 10.1007/BF02341614. [DOI] [PubMed] [Google Scholar]
  4. Bosma G. C., Fried M., Custer R. P., Carroll A., Gibson D. M., Bosma M. J. Evidence of functional lymphocytes in some (leaky) scid mice. J Exp Med. 1988 Mar 1;167(3):1016–1033. doi: 10.1084/jem.167.3.1016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Boyd Y., Fraser N. J. Methylation patterns at the hypervariable X-chromosome locus DXS255 (M27 beta): correlation with X-inactivation status. Genomics. 1990 Jun;7(2):182–187. doi: 10.1016/0888-7543(90)90539-7. [DOI] [PubMed] [Google Scholar]
  6. Carroll A. M., Bosma M. J. T-lymphocyte development in scid mice is arrested shortly after the initiation of T-cell receptor delta gene recombination. Genes Dev. 1991 Aug;5(8):1357–1366. doi: 10.1101/gad.5.8.1357. [DOI] [PubMed] [Google Scholar]
  7. Conley M. E., Lavoie A., Briggs C., Brown P., Guerra C., Puck J. M. Nonrandom X chromosome inactivation in B cells from carriers of X chromosome-linked severe combined immunodeficiency. Proc Natl Acad Sci U S A. 1988 May;85(9):3090–3094. doi: 10.1073/pnas.85.9.3090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Coulombel L., Eaves A. C., Eaves C. J. Enzymatic treatment of long-term human marrow cultures reveals the preferential location of primitive hemopoietic progenitors in the adherent layer. Blood. 1983 Aug;62(2):291–297. [PubMed] [Google Scholar]
  9. Fogh J. Cultivation, characterization, and identification of human tumor cells with emphasis on kidney, testis, and bladder tumors. Natl Cancer Inst Monogr. 1978 Dec;(49):5–9. [PubMed] [Google Scholar]
  10. Fulop G. M., Phillips R. A. The scid mutation in mice causes a general defect in DNA repair. Nature. 1990 Oct 4;347(6292):479–482. doi: 10.1038/347479a0. [DOI] [PubMed] [Google Scholar]
  11. Griscelli C., Durandy A., Virelizier J. L., Ballet J. J., Daguillard F. Selective defect of precursor T cells associated with apparently normal B lymphocytes in severe combined immunodeficiency disease. J Pediatr. 1978 Sep;93(3):404–411. doi: 10.1016/s0022-3476(78)81146-9. [DOI] [PubMed] [Google Scholar]
  12. Hendrickson E. A., Qin X. Q., Bump E. A., Schatz D. G., Oettinger M., Weaver D. T. A link between double-strand break-related repair and V(D)J recombination: the scid mutation. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4061–4065. doi: 10.1073/pnas.88.10.4061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Le Deist F., Thoenes G., Corado J., Lisowska-Grospierre B., Fischer A. Immunodeficiency with low expression of the T cell receptor/CD3 complex. Effect on T lymphocyte activation. Eur J Immunol. 1991 Jul;21(7):1641–1647. doi: 10.1002/eji.1830210709. [DOI] [PubMed] [Google Scholar]
  14. Lefranc M. P., Rabbitts T. H. Two tandemly organized human genes encoding the T-cell gamma constant-region sequences show multiple rearrangement in different T-cell types. Nature. 1985 Aug 1;316(6027):464–466. doi: 10.1038/316464a0. [DOI] [PubMed] [Google Scholar]
  15. Papadopoulo D., Averbeck D., Moustacchi E. The fate of 8-methoxypsoralen-photoinduced DNA interstrand crosslinks in Fanconi's anemia cells of defined genetic complementation groups. Mutat Res. 1987 Nov;184(3):271–280. doi: 10.1016/0167-8817(87)90026-5. [DOI] [PubMed] [Google Scholar]
  16. Phillips R. A., Spaner D. E. The scid mouse: mutation in a DNA repair gene creates recipients useful for studies on stem cells, lymphocyte development and graft-versus-host disease. Immunol Rev. 1991 Dec;124:63–74. doi: 10.1111/j.1600-065x.1991.tb00616.x. [DOI] [PubMed] [Google Scholar]
  17. Schwarz K., Hansen-Hagge T. E., Knobloch C., Friedrich W., Kleihauer E., Bartram C. R. Severe combined immunodeficiency (SCID) in man: B cell-negative (B-) SCID patients exhibit an irregular recombination pattern at the JH locus. J Exp Med. 1991 Nov 1;174(5):1039–1048. doi: 10.1084/jem.174.5.1039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Senn J. S., McCulloch E. A. Radiation sensitivity of human bone marrow cells measured by a cell culture method. Blood. 1970 Jan;35(1):56–60. [PubMed] [Google Scholar]
  19. Swift M. Genetic aspects of ataxia-telangiectasia. Immunodefic Rev. 1990;2(1):67–81. [PubMed] [Google Scholar]
  20. Taylor A. M., Harnden D. G., Arlett C. F., Harcourt S. A., Lehmann A. R., Stevens S., Bridges B. A. Ataxia telangiectasia: a human mutation with abnormal radiation sensitivity. Nature. 1975 Dec 4;258(5534):427–429. doi: 10.1038/258427a0. [DOI] [PubMed] [Google Scholar]
  21. Yanagi Y., Chan A., Chin B., Minden M., Mak T. W. Analysis of cDNA clones specific for human T cells and the alpha and beta chains of the T-cell receptor heterodimer from a human T-cell line. Proc Natl Acad Sci U S A. 1985 May;82(10):3430–3434. doi: 10.1073/pnas.82.10.3430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. de Saint-Basile G., Le Deist F., de Villartay J. P., Cerf-Bensussan N., Journet O., Brousse N., Griscelli C., Fischer A. Restricted heterogeneity of T lymphocytes in combined immunodeficiency with hypereosinophilia (Omenn's syndrome). J Clin Invest. 1991 Apr;87(4):1352–1359. doi: 10.1172/JCI115139. [DOI] [PMC free article] [PubMed] [Google Scholar]

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