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. 1978 Nov;34(2):260–267.

Severe combined immunodeficiency disease: a model of T-cell dysfunction.

H M Dosch, J W Lee, E W Gelfand, J A Falk
PMCID: PMC1537483  PMID: 367653

Abstract

Studies in three patients with severe combined immunodeficiency disease (SCID) and normal adenosine deaminase demonstrated that the combined defect of both T- and B-lymphocyte function may reflect the lack of normal maturation of thymic epithelial cells. This results in the failure of initiation of T-cell differentiation and consequent failure of T-cell dependent maturation of B-lymphocytes to an antibody-secreting stage. SCID B lymphocytes were shown to be capable of generating a specific IgM-antibody response to two T-cell-dependent antigens in vitro under either of the following conditions: (a) provision of autologous T-helper cells which were induced following incubation of precursor cells on monolayers of cultured human thymic epithelium or (b) in the presence of allogeneic T-helper cells. Specific IgM anti-ovalbumin (OA) responses were also generated in the absence of provided T-helper cells when the antigen was insolubilized (Sepharose-OA). The antibody-secreting cells and their circulating precursors carried surface IgM, HLA and Ia-like determinants and proliferated in response to antigen. Identification of this form of SCID may be important when considering therapy and provides an excellent model for the study of the T-cell-dependent acquisition and expression of B-cell immunity.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bergholtz B. O., Thorsby E. Macrophage-dependent response of immune human T lymphocytes to PPD in vitro. Influence of HLA-D histocompatibility. Scand J Immunol. 1977;6(8):779–786. doi: 10.1111/j.1365-3083.1977.tb02151.x. [DOI] [PubMed] [Google Scholar]
  2. Buckley R. H., Gilbertsen R. B., Schiff R. I., Ferreira E., Sanal S. O., Waldmann T. A. Heterogeneity of lymphocyte subpopulations in severe combined immunodeficiency. Evidence against a stem cell defect. J Clin Invest. 1976 Jul;58(1):130–136. doi: 10.1172/JCI108441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dosch H-M, Gelfand E. W. Generation of human plaque-forming cells in culture: tissue distribution, antigenic and cellular requirements. J Immunol. 1977 Jan;118(1):302–308. [PubMed] [Google Scholar]
  4. Dosch H. M., Gelfand E. W. In vitro induction and measurement of hemolytic plaque forming cells in man. J Immunol Methods. 1976;11(2):107–116. doi: 10.1016/0022-1759(76)90138-1. [DOI] [PubMed] [Google Scholar]
  5. Dosch H. M., Percy M. E., Gelfand E. W. Functional differentiation of B lymphocytes in congenital agammaglobulinemia. I. Generation of hemolytic plaque-forming cells. J Immunol. 1977 Dec;119(6):1959–1964. [PubMed] [Google Scholar]
  6. Fauci A. S., Pratt K. R. Activation of human B lymphocytes. I. Direct plaque-forming cell assay for the measurement of polyclonal activation and antigenic stimulation of human B lymphocytes. J Exp Med. 1976 Sep 1;144(3):674–684. doi: 10.1084/jem.144.3.674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gelfand E. W., Biggar W. D., Orange R. P. Immune deficiency: evaluation, diagnosis, and therapy. Pediatr Clin North Am. 1974 Nov;21(4):745–776. doi: 10.1016/s0031-3955(16)33060-7. [DOI] [PubMed] [Google Scholar]
  8. Giblett E. R., Anderson J. E., Cohen F., Pollara B., Meuwissen H. J. Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity. Lancet. 1972 Nov 18;2(7786):1067–1069. doi: 10.1016/s0140-6736(72)92345-8. [DOI] [PubMed] [Google Scholar]
  9. Hammerling U., Chin A. F., Abbott J., Scheid M. P. The ontogeny of murine B lymphocytes. I. Induction of phenotypic conversion of Ia-to Ia+ lymphocytes. J Immunol. 1975 Nov;115(5):1425–1431. [PubMed] [Google Scholar]
  10. Hong R., Santosham M., Schulte-Wissermann H., Horowitz S., Hsu S. H., Winkelstein J. A. Reconstitution of B and T lymphocyte function in severe combined immunodeficiency disease after transplantation with thymic epithelium. Lancet. 1976 Dec 11;2(7998):1270–1272. doi: 10.1016/s0140-6736(76)92031-6. [DOI] [PubMed] [Google Scholar]
  11. Insel R. A., Merler E. The necessity for T cell help for human tonsil B cell responses to pokeweed mitogens: induction of DNA synthesis, immunoglobulin, and specific antibody production with a T cell helper factor produced with pokeweed mitogen. J Immunol. 1977 Jun;118(6):2009–2014. [PubMed] [Google Scholar]
  12. Katz D. H. The allogeneic effect on immune responses: model for regulatory influences of T lymphocytes on the immune system. Transplant Rev. 1972;12:141–179. doi: 10.1111/j.1600-065x.1972.tb00055.x. [DOI] [PubMed] [Google Scholar]
  13. Klein J. List of congenic lines of mice. I. Lines with differences at alloantigen loci. Transplantation. 1973 Jan;15(1):137–153. doi: 10.1097/00007890-197301000-00021. [DOI] [PubMed] [Google Scholar]
  14. Muchmore A. V., Koski I., Dooley N., Blaese R. M. Artifactual plaque formation in vitro and in vivo to passive transfer of specific antibody. J Immunol. 1976 Apr;116(4):1016–1019. [PubMed] [Google Scholar]
  15. Möller G. One non-specific signal triggers b lymphocytes. Transplant Rev. 1975;23:126–137. [PubMed] [Google Scholar]
  16. Pantelouris E. M. Observations on the immunobiology of 'nude' mice. Immunology. 1971 Feb;20(2):247–252. [PMC free article] [PubMed] [Google Scholar]
  17. Percy M. E., Dosch H. M., Gelfand E. W. Functional differentiation of B lymphocytes in congenital agammaglobulinemia. II. Immunochemical analysis of the in vitro primary immune response. J Immunol. 1977 Dec;119(6):1965–1972. [PubMed] [Google Scholar]
  18. Pyke K. W., Dosch H., Ipp M. M., Gelfand E. W. Demonstration of an intrathymic defect in a case of severe combined immunodeficiency disease. N Engl J Med. 1975 Aug 28;293(9):424–428. doi: 10.1056/NEJM197508282930904. [DOI] [PubMed] [Google Scholar]
  19. Pyke K. W., Gelfand E. W. Morphological and functional maturation of human thymic epithelium in culture. Nature. 1974 Oct 4;251(5474):421–423. doi: 10.1038/251421a0. [DOI] [PubMed] [Google Scholar]
  20. Seeger R. C., Robins R. A., Stevens R. H., Klein R. B., Waldman D. J., Zeltzer P. M., Kessler S. W. Severe combined immunodeficiency with B lymphocytes: in vitro correction of defective immunoglobulin production by addition of normal T lymphocytes. Clin Exp Immunol. 1976 Oct;26(1):1–10. [PMC free article] [PubMed] [Google Scholar]
  21. Swain S. L., Dutton R. W. Negative allogeneic effects in vitro. I. Allogeneic T cells markedly suppress the secondary antibody-forming cell response. J Immunol. 1977 Jun;118(6):2262–2268. [PubMed] [Google Scholar]

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