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. 1994 Feb;95(2):209–214. doi: 10.1111/j.1365-2249.1994.tb06512.x

The costimulatory signal CD28 is fully functional but cannot correct the impaired antigen response in T cells of patients with common variable immunodeficiency.

M B Fischer 1, H M Wolf 1, H Eggenbauer 1, V Thon 1, E Vogel 1, J Lokaj 1, J Litzman 1, J W Mannhalter 1, M M Eibl 1
PMCID: PMC1534938  PMID: 8306493

Abstract

A wide spectrum of different immunologic abnormalities have been postulated as being responsible for the impairment of specific antibody production and the decrease in all or selected immunoglobulin isotypes present in common variable immunodeficiency (CVID). These abnormalities include impaired B cell differentiation and/or function, defective macrophage function, and significant T cell defects. The aim of the present study was to delineate whether the accessory molecule CD28 is involved in the impaired antigen response of T cells from patients with CVID. Our results demonstrate that CD28 costimulation was functional in T cells stimulated with anti-CD3 or anti-TCR MoAb, but could not correct the impaired response of patients' peripheral blood T cells to tetanus toxoid. Analysis of patients' long-term cultured T cells further confirmed these results. Exogenous rIL-2, another costimulus, augmented but did not correct the defective proliferation and lymphokine production in patients' antigen-driven peripheral blood T lymphocytes or in long-term cultured T cells. These findings indicate that the CD28 signalling pathway in these patients' T cells is unimpaired, and that costimulation via CD28 cannot correct the defect occurring in the course of TCR-mediated T cell activation.

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Selected References

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  1. Baumert E., Wolff-Vorbeck G., Schlesier M., Peter H. H. Immunophenotypical alterations in a subset of patients with common variable immunodeficiency (CVID). Clin Exp Immunol. 1992 Oct;90(1):25–30. doi: 10.1111/j.1365-2249.1992.tb05826.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bryant A., Calver N. C., Toubi E., Webster A. D., Farrant J. Classification of patients with common variable immunodeficiency by B cell secretion of IgM and IgG in response to anti-IgM and interleukin-2. Clin Immunol Immunopathol. 1990 Aug;56(2):239–248. doi: 10.1016/0090-1229(90)90145-g. [DOI] [PubMed] [Google Scholar]
  3. Eibl M. M., Mannhalter J. W., Zielinski C. C., Ahmad R. Defective macrophage--T-cell interaction in common varied immunodeficiency. Clin Immunol Immunopathol. 1982 Mar;22(3):316–322. doi: 10.1016/0090-1229(82)90048-4. [DOI] [PubMed] [Google Scholar]
  4. Eibl M. M., Mannhalter J. W., Zlabinger G., Mayr W. R., Tilz G. P., Ahmad R., Zielinski C. C. Defective macrophage function in a patient with common variable immunodeficiency. N Engl J Med. 1982 Sep 23;307(13):803–806. doi: 10.1056/NEJM198209233071307. [DOI] [PubMed] [Google Scholar]
  5. Fiedler W., Sykora K. W., Welte K., Kolitz J. E., Cunningham-Rundles C., Holloway K., Miller G. A., Souza L., Mertelsmann R. T-cell activation defect in common variable immunodeficiency: restoration by phorbol myristate acetate (PMA) or allogeneic macrophages. Clin Immunol Immunopathol. 1987 Aug;44(2):206–218. doi: 10.1016/0090-1229(87)90066-3. [DOI] [PubMed] [Google Scholar]
  6. Fischer M. B., Hauber I., Vogel E., Wolf H. M., Mannhalter J. W., Eibl M. M. Defective interleukin-2 and interferon-gamma gene expression in response to antigen in a subgroup of patients with common variable immunodeficiency. J Allergy Clin Immunol. 1993 Aug;92(2):340–352. doi: 10.1016/0091-6749(93)90178-i. [DOI] [PubMed] [Google Scholar]
  7. Fraser J. D., Weiss A. Regulation of T-cell lymphokine gene transcription by the accessory molecule CD28. Mol Cell Biol. 1992 Oct;12(10):4357–4363. doi: 10.1128/mcb.12.10.4357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gillis S., Smith K. A. Long term culture of tumour-specific cytotoxic T cells. Nature. 1977 Jul 14;268(5616):154–156. doi: 10.1038/268154a0. [DOI] [PubMed] [Google Scholar]
  9. Jenkins M. K., Taylor P. S., Norton S. D., Urdahl K. B. CD28 delivers a costimulatory signal involved in antigen-specific IL-2 production by human T cells. J Immunol. 1991 Oct 15;147(8):2461–2466. [PubMed] [Google Scholar]
  10. Jenkins M. K. The role of cell division in the induction of clonal anergy. Immunol Today. 1992 Feb;13(2):69–73. doi: 10.1016/0167-5699(92)90137-V. [DOI] [PubMed] [Google Scholar]
  11. June C. H., Ledbetter J. A., Lindsten T., Thompson C. B. Evidence for the involvement of three distinct signals in the induction of IL-2 gene expression in human T lymphocytes. J Immunol. 1989 Jul 1;143(1):153–161. [PubMed] [Google Scholar]
  12. June C. H., Ledbetter J. A., Linsley P. S., Thompson C. B. Role of the CD28 receptor in T-cell activation. Immunol Today. 1990 Jun;11(6):211–216. doi: 10.1016/0167-5699(90)90085-n. [DOI] [PubMed] [Google Scholar]
  13. LaSalle J. M., Tolentino P. J., Freeman G. J., Nadler L. M., Hafler D. A. Early signaling defects in human T cells anergized by T cell presentation of autoantigen. J Exp Med. 1992 Jul 1;176(1):177–186. doi: 10.1084/jem.176.1.177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Linsley P. S., Ledbetter J. A. The role of the CD28 receptor during T cell responses to antigen. Annu Rev Immunol. 1993;11:191–212. doi: 10.1146/annurev.iy.11.040193.001203. [DOI] [PubMed] [Google Scholar]
  15. Mogensen C. E. The glomerular permeability determined by dextran clearance using Sephadex gel filtration. Scand J Clin Lab Invest. 1968;21(1):77–82. doi: 10.3109/00365516809076979. [DOI] [PubMed] [Google Scholar]
  16. Nakagawa T., Hirano T., Nakagawa N., Yoshizaki K., Kishimoto T. Effect of recombinant IL 2 and gamma-IFN on proliferation and differentiation of human B cells. J Immunol. 1985 Feb;134(2):959–966. [PubMed] [Google Scholar]
  17. North M. E., Spickett G. P., Allsop J., Webster A. D., Farrant J. Defective DNA synthesis by T cells in acquired 'common-variable' hypogammaglobulinaemia on stimulation with mitogens. Clin Exp Immunol. 1989 Apr;76(1):19–23. [PMC free article] [PubMed] [Google Scholar]
  18. North M. E., Webster A. D., Farrant J. Role of interleukin-2 and interleukin-6 in the mitogen responsiveness of T cells from patients with 'common-variable' hypogammaglobulinaemia. Clin Exp Immunol. 1990 Sep;81(3):412–416. doi: 10.1111/j.1365-2249.1990.tb05348.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pastorelli G., Roncarolo M. G., Touraine J. L., Peronne G., Tovo P. A., de Vries J. E. Peripheral blood lymphocytes of patients with common variable immunodeficiency (CVI) produce reduced levels of interleukin-4, interleukin-2 and interferon-gamma, but proliferate normally upon activation by mitogens. Clin Exp Immunol. 1989 Dec;78(3):334–340. [PMC free article] [PubMed] [Google Scholar]
  20. Pellegrino M. A., Ferrone S., Theofilopoulos A. N. Isolation of human T and B lymphocytes by rosette formation with 2-aminoethylisothiquronium bromide (AET) -treated sheep red blood cells with monkey red blood cells. J Immunol Methods. 1976;11(3-4):273–279. doi: 10.1016/0022-1759(76)90120-4. [DOI] [PubMed] [Google Scholar]
  21. Saiki O., Ralph P., Cunningham-Rundles C., Good R. A. Three distinct stages of B-cell defects in common varied immunodeficiency. Proc Natl Acad Sci U S A. 1982 Oct;79(19):6008–6012. doi: 10.1073/pnas.79.19.6008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sneller M. C., Strober W. Abnormalities of lymphokine gene expression in patients with common variable immunodeficiency. J Immunol. 1990 May 15;144(10):3762–3769. [PubMed] [Google Scholar]
  23. Thompson C. B., Lindsten T., Ledbetter J. A., Kunkel S. L., Young H. A., Emerson S. G., Leiden J. M., June C. H. CD28 activation pathway regulates the production of multiple T-cell-derived lymphokines/cytokines. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1333–1337. doi: 10.1073/pnas.86.4.1333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Waldmann T. A., Durm M., Broder S., Blackman M., Blaese R. M., Strober W. Role of suppressor T cells in pathogenesis of common variable hypogammaglobulinaemia. Lancet. 1974 Sep 14;2(7881):609–613. doi: 10.1016/s0140-6736(74)91940-0. [DOI] [PubMed] [Google Scholar]
  25. Wright J. J., Wagner D. K., Blaese R. M., Hagengruber C., Waldmann T. A., Fleisher T. A. Characterization of common variable immunodeficiency: identification of a subset of patients with distinctive immunophenotypic and clinical features. Blood. 1990 Nov 15;76(10):2046–2051. [PubMed] [Google Scholar]

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