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. 1992 Aug;89(2):198–203. doi: 10.1111/j.1365-2249.1992.tb06932.x

T cell heterogeneity in patients with common variable immunodeficiency as assessed by abnormalities of T cell subpopulations and T cell receptor gene analysis.

F Pandolfi 1, L Trentin 1, J E San Martin 1, J T Wong 1, J T Kurnick 1, R A Moscicki 1
PMCID: PMC1554438  PMID: 1638763

Abstract

T lymphocyte regulation of immunoglobulin production may be abnormal in some patients with common variable immunodeficiency (CVI). Phenotypic analysis of peripheral blood T lymphocytes from nine patients with CVI was conducted to examine whether an abnormal distribution could be detected in a functionally distinct T lymphocyte subpopulation. The percentage of CD8+ lymphocytes proved to be increased in some patients and decreased in others. In comparison with normal controls, many patients with CVI had reduced percentages of lymphocytes expressing both CD4 and CD45RA, a phenotype associate with naive CD4+ cells. There was no significant difference in CD4+ populations bearing CD29 or leucocyte adhesion molecule-1 (LAM-1) antigens. The pattern of gene rearrangement of the T cell antigen receptor (TCR) was studied using peripheral blood lymphocytes from these patients with CVI. Genomic DNA from freshly isolated lymphocytes as well as from selectively propagated CD4+ or CD8+ populations were examined using Southern blot analysis and a probe for the beta chain of the TCR. A polyclonal pattern of TCR gene rearrangement, without the appearance of dominant non-germline bands, was demonstrated in all patient samples. These data suggest that the T lymphocytes in patients with CVI have a polyclonal pattern of TCR rearrangement despite an abnormal distribution of T cell subpopulations in some patients.

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Selected References

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  1. Camerini D., James S. P., Stamenkovic I., Seed B. Leu-8/TQ1 is the human equivalent of the Mel-14 lymph node homing receptor. Nature. 1989 Nov 2;342(6245):78–82. doi: 10.1038/342078a0. [DOI] [PubMed] [Google Scholar]
  2. Cunningham-Rundles C. Clinical and immunologic analyses of 103 patients with common variable immunodeficiency. J Clin Immunol. 1989 Jan;9(1):22–33. doi: 10.1007/BF00917124. [DOI] [PubMed] [Google Scholar]
  3. Durham J. C., Stephens D. S., Rimland D., Nassar V. H., Spira T. J. Common variable hypogammaglobulinemia complicated by an unusual T-suppressor/cytotoxic cell lymphoma. Cancer. 1987 Jan 15;59(2):271–276. doi: 10.1002/1097-0142(19870115)59:2<271::aid-cncr2820590216>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
  4. Frenkel J., Neijens H. J., den Hollander J. C., Wolvers-Tettero I. L., van Dongen J. J. Oligoclonal T cell proliferative disorder in combined immunodeficiency. Pediatr Res. 1988 Nov;24(5):622–627. doi: 10.1203/00006450-198811000-00017. [DOI] [PubMed] [Google Scholar]
  5. Greally J. F., Lawlor E., Lyons J., Rickinson A., Sakamoto K., Purtilo D. Acquired hypogammaglobulinemia following infectious mononucleosis. J Clin Immunol. 1983 Jul;3(3):207–211. doi: 10.1007/BF00915344. [DOI] [PubMed] [Google Scholar]
  6. Hafler D. A., Duby A. D., Lee S. J., Benjamin D., Seidman J. G., Weiner H. L. Oligoclonal T lymphocytes in the cerebrospinal fluid of patients with multiple sclerosis. J Exp Med. 1988 Apr 1;167(4):1313–1322. doi: 10.1084/jem.167.4.1313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Lanning M., Kouvalainen K., Similä S., Raunio V. Agammaglobulinemia with arthritis and celiac disease developing after infectious mononucleosis. Follow-up study of a case. Scand J Infect Dis. 1977;9(2):144–148. doi: 10.3109/inf.1977.9.issue-2.18. [DOI] [PubMed] [Google Scholar]
  8. Lebranchu Y., Thibault G., Degenne D., Bardos P. Deficiency of CD4+CD45R+ T lymphocytes in common variable immunodeficiency. N Engl J Med. 1990 Jul 26;323(4):276–277. doi: 10.1056/NEJM199007263230416. [DOI] [PubMed] [Google Scholar]
  9. Miceli M. C., Finn O. J. T cell receptor beta-chain selection in human allograft rejection. J Immunol. 1989 Jan 1;142(1):81–86. [PubMed] [Google Scholar]
  10. Minden M. D., Toyonaga B., Ha K., Yanagi Y., Chin B., Gelfand E., Mak T. Somatic rearrangement of T-cell antigen receptor gene in human T-cell malignancies. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1224–1227. doi: 10.1073/pnas.82.4.1224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Moebius U., Manns M., Hess G., Kober G., Meyer zum Büschenfelde K. H., Meuer S. C. T cell receptor gene rearrangements of T lymphocytes infiltrating the liver in chronic active hepatitis B and primary biliary cirrhosis (PBC): oligoclonality of PBC-derived T cell clones. Eur J Immunol. 1990 Apr;20(4):889–896. doi: 10.1002/eji.1830200426. [DOI] [PubMed] [Google Scholar]
  12. Morimoto C., Letvin N. L., Boyd A. W., Hagan M., Brown H. M., Kornacki M. M., Schlossman S. F. The isolation and characterization of the human helper inducer T cell subset. J Immunol. 1985 Jun;134(6):3762–3769. [PubMed] [Google Scholar]
  13. Morimoto C., Letvin N. L., Distaso J. A., Aldrich W. R., Schlossman S. F. The isolation and characterization of the human suppressor inducer T cell subset. J Immunol. 1985 Mar;134(3):1508–1515. [PubMed] [Google Scholar]
  14. Moscicki R. A., Morison W. L., Parrish J. A., Bloch K. J., Colvin R. B. Reduction of the fraction of circulating helper-inducer T cells identified by monoclonal antibodies in psoriatic patients treated with long-term psoralen/ultraviolet-A radiation (PUVA). J Invest Dermatol. 1982 Sep;79(3):205–208. doi: 10.1111/1523-1747.ep12500058. [DOI] [PubMed] [Google Scholar]
  15. Pandolfi F., Corte G., Quinti I., Fiorilli M., Frieligsdorf A., Bargellesi A., Aiuti F. Defect of T helper lymphocytes, as identified by the 5/9 monoclonal antibody, in patients with common variable hypogammaglobulinaemia. Clin Exp Immunol. 1983 Mar;51(3):470–474. [PMC free article] [PubMed] [Google Scholar]
  16. Pandolfi F., Quinti I., Frielingsdorf A., Goldstein G., Businco L., Aiuti F. Abnormalities of regulatory T-cell subpopulations in patients with primary immunoglobulin deficiencies. Clin Immunol Immunopathol. 1982 Mar;22(3):323–330. doi: 10.1016/0090-1229(82)90049-6. [DOI] [PubMed] [Google Scholar]
  17. Pandolfi F., Strong D. M., Slease R. B., Bonnard G. D. Serological and functional characterization of human T cell subsets. Clin Exp Immunol. 1981 Feb;43(2):319–328. [PMC free article] [PubMed] [Google Scholar]
  18. Provisor A. J., Iacuone J. J., Chilcote R. R., Neiburger R. G., Crussi F. G. Acquired agammaglobulinemia after a life-threatening illness with clinical and laboratory features of infectious mononucleosis in three related male children. N Engl J Med. 1975 Jul 10;293(2):62–65. doi: 10.1056/NEJM197507102930202. [DOI] [PubMed] [Google Scholar]
  19. Purtilo D. T., Zelkowitz L., Harada S., Brooks C. D., Bechtold T., Lipscomb H., Yetz J., Rogers G. Delayed onset of infectious mononucleosis associated with acquired agammaglobulinemia and red cell aplasia. Ann Intern Med. 1984 Aug;101(2):180–186. doi: 10.7326/0003-4819-101-2-180. [DOI] [PubMed] [Google Scholar]
  20. Reinherz E. L., Cooper M. D., Schlossman S. F., Rosen F. S. Abnormalities of T cell maturation and regulation in human beings with immunodeficiency disorders. J Clin Invest. 1981 Sep;68(3):699–705. doi: 10.1172/JCI110305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rodriguez M. A., Bankhurst A. D., Williams R. C., Jr Characterization of the suppressor activity in lymphocytes from patients with common variable hypogammaglobulinemia: evidence for an associated primary B-cell defect. Clin Immunol Immunopathol. 1983 Oct;29(1):35–50. doi: 10.1016/0090-1229(83)90005-3. [DOI] [PubMed] [Google Scholar]
  22. Rubinstein A., Sicklick M., Mehra V., Rosen F. S., Levey R. H. Antihelper T cell autoantibody in acquired agammaglobulinemia. J Clin Invest. 1981 Jan;67(1):42–50. doi: 10.1172/JCI110031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Sanders M. E., Makgoba M. W., Shaw S. Human naive and memory T cells: reinterpretation of helper-inducer and suppressor-inducer subsets. Immunol Today. 1988 Jul-Aug;9(7-8):195–199. doi: 10.1016/0167-5699(88)91212-1. [DOI] [PubMed] [Google Scholar]
  25. Siegal F. P., Siegal M., Good R. A. Suppression of B-cell differentiation by leukocytes from hypogammaglobulinemic patients. J Clin Invest. 1976 Jul;58(1):109–122. doi: 10.1172/JCI108439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Stamenkovic I., Stegagno M., Wright K. A., Krane S. M., Amento E. P., Colvin R. B., Duquesnoy R. J., Kurnick J. T. Clonal dominance among T-lymphocyte infiltrates in arthritis. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1179–1183. doi: 10.1073/pnas.85.4.1179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Stohl W., Cunningham-Rundles C., Mayer L. In vitro induction of T cell-dependent B cell differentiation in patients with common varied immunodeficiency. Clin Immunol Immunopathol. 1988 Nov;49(2):273–282. doi: 10.1016/0090-1229(88)90117-1. [DOI] [PubMed] [Google Scholar]
  29. Tedder T. F., Penta A. C., Levine H. B., Freedman A. S. Expression of the human leukocyte adhesion molecule, LAM1. Identity with the TQ1 and Leu-8 differentiation antigens. J Immunol. 1990 Jan 15;144(2):532–540. [PubMed] [Google Scholar]
  30. 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]
  31. Wen T., Mellstedt H., Jondal M. Presence of clonal T cell populations in chronic B lymphocytic leukemia and smoldering myeloma. J Exp Med. 1990 Mar 1;171(3):659–666. doi: 10.1084/jem.171.3.659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wong J. T., Pinto C. E., Gifford J. D., Kurnick J. T., Kradin R. L. Characterization of the CD4+ and CD8+ tumor infiltrating lymphocytes propagated with bispecific monoclonal antibodies. J Immunol. 1989 Nov 15;143(10):3404–3411. [PubMed] [Google Scholar]
  33. Yoshikai Y., Anatoniou D., Clark S. P., Yanagi Y., Sangster R., Van den Elsen P., Terhorst C., Mak T. W. Sequence and expression of transcripts of the human T-cell receptor beta-chain genes. Nature. 1984 Dec 6;312(5994):521–524. doi: 10.1038/312521a0. [DOI] [PubMed] [Google Scholar]

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