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. 1988 May 1;167(5):1523–1534. doi: 10.1084/jem.167.5.1523

Autoreactive T cell clones specific for class I and class II HLA antigens isolated from a human chimera

PMCID: PMC2188931  PMID: 3284961

Abstract

T cell clones of donor origin that specifically react with recipient cells were obtained from a SCID patient successfully reconstituted by allogeneic fetal liver and thymus transplantation performed 10 yr ago. The majority of these clones displayed both cytotoxic and proliferative responses towards PBL and an EBV-transformed B cell line derived from the patient. In addition, these T cell clones had proliferative and cytotoxic responses towards the parental PBL, EBV cell lines, and PHA blasts. Blocking studies with anti-class I and anti-class II HLA mAbs indicated that the activity of the CD4+ T cell clones was specifically directed against class II HLA antigens of the recipient. On the other hand, the cytotoxic and proliferative responses of the CD8+ T cell clones were specific for class I HLA antigens which are ubiquitously expressed on the recipient cells. Thus, the establishment of transplantation tolerance observed in this stable human chimera is not due to the elimination of host-reactive T cells from the repertoire and suggests the presence of a peripheral autoregulatory suppressor mechanism.

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Selected References

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

  1. Bensussan A., Meuer S. C., Schlossman S. F., Reinherz E. L. Delineation of an immunoregulatory amplifier population recognizing autologous Ia molecules. Analysis with human T cell clones. J Exp Med. 1984 Feb 1;159(2):559–576. doi: 10.1084/jem.159.2.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Betuel H., Gebuhrer L., Lambert J., Freidel A. C., Farre A. A possible new HLA-DR allele. Hum Immunol. 1983 Nov;8(3):227–237. doi: 10.1016/0198-8859(83)90040-x. [DOI] [PubMed] [Google Scholar]
  3. Claësson M. H., Miller R. G. Functional heterogeneity in allospecific cytotoxic T lymphocyte clones. I. CTL clones express strong anti-self suppressive activity. J Exp Med. 1984 Dec 1;160(6):1702–1716. doi: 10.1084/jem.160.6.1702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hilgert I. The involvement of activated specific suppressor T cells in maintenance of transplantation tolerance. Immunol Rev. 1979;46:27–53. doi: 10.1111/j.1600-065x.1979.tb00283.x. [DOI] [PubMed] [Google Scholar]
  5. Hohlfeld R., Toyka K. V., Heininger K., Grosse-Wilde H., Kalies I. Autoimmune human T lymphocytes specific for acetylcholine receptor. Nature. 1984 Jul 19;310(5974):244–246. doi: 10.1038/310244a0. [DOI] [PubMed] [Google Scholar]
  6. Hutchinson I. V. Suppressor T cells in allogeneic models. Transplantation. 1986 May;41(5):547–555. doi: 10.1097/00007890-198605000-00001. [DOI] [PubMed] [Google Scholar]
  7. Kappler J. W., Roehm N., Marrack P. T cell tolerance by clonal elimination in the thymus. Cell. 1987 Apr 24;49(2):273–280. doi: 10.1016/0092-8674(87)90568-x. [DOI] [PubMed] [Google Scholar]
  8. Leung D. Y., Young M. C., Geha R. S. Induction of IgG and IgE synthesis in normal B cells by autoreactive T cell clones. J Immunol. 1986 Apr 15;136(8):2851–2855. [PubMed] [Google Scholar]
  9. O'Reilly R. J., Kapoor N., Kirkpatrick D., Flomenberg N., Pollack M. S., Dupont B., Good R. A., Reisner Y. Transplantation of hematopoietic cells for lethal congenital immunodeficiencies. Birth Defects Orig Artic Ser. 1983;19(3):129–137. [PubMed] [Google Scholar]
  10. Quaranta V., Walker L. E., Pellegrino M. A., Ferrone S. Purification of immunologically functional subsets of human Ia-like antigens on a monoclonal antibody (Q5/13) immunoadsorbent. J Immunol. 1980 Oct;125(4):1421–1425. [PubMed] [Google Scholar]
  11. Roncarolo M. G., Touraine J. L., Banchereau J. Cooperation between major histocompatibility complex mismatched mononuclear cells from a human chimera in the production of antigen-specific antibody. J Clin Invest. 1986 Mar;77(3):673–680. doi: 10.1172/JCI112361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Rosenkrantz K., Dupont B., Williams D., Flomenberg N. Autocytotoxic and autosuppressor T-cell lines generated from autologous lymphocyte cultures. Hum Immunol. 1987 Jul;19(3):189–203. doi: 10.1016/0198-8859(87)90069-3. [DOI] [PubMed] [Google Scholar]
  13. Spits H., Keizer G., Borst J., Terhorst C., Hekman A., de Vries J. E. Characterization of monoclonal antibodies against cell surface molecules associated with cytotoxic activity of natural and activated killer cells and cloned CTL lines. Hybridoma. 1983;2(4):423–437. doi: 10.1089/hyb.1983.2.423. [DOI] [PubMed] [Google Scholar]
  14. Strober S., Palathumpat V., Schwadron R., Hertel-Wulff B. Cloned natural suppressor cells prevent lethal graft-vs-host disease. J Immunol. 1987 Feb 1;138(3):699–703. [PubMed] [Google Scholar]
  15. Tilkin A. F., Michon J., Juy D., Kayibanda M., Henin Y., Sterkers G., Betuel H., Lévy J. P. Autoreactive T cell clones of MHC class II specificities are produced during responses against foreign antigens in man. J Immunol. 1987 Feb 1;138(3):674–679. [PubMed] [Google Scholar]
  16. Touraine J. L. Bone-marrow and fetal-liver transplantation in immunodeficiencies and inborn errors of metabolism: lack of significant restriction of T-cell function in long-term chimeras despite HLA-mismatch. Immunol Rev. 1983;71:103–121. doi: 10.1111/j.1600-065x.1983.tb01070.x. [DOI] [PubMed] [Google Scholar]
  17. Touraine J. L., Bétuel H. Immunodeficiency diseases and expression of HLA antigens. Hum Immunol. 1981 Mar;2(2):147–153. doi: 10.1016/0198-8859(81)90061-6. [DOI] [PubMed] [Google Scholar]
  18. Tutschka P. J., Hess A. D., Beschorner W. E., Santos G. W. Suppressor cells in transplantation tolerance. III. The role of antigen in the maintenance of transplantation tolerance. Transplantation. 1982 May;33(5):510–514. doi: 10.1097/00007890-198205000-00009. [DOI] [PubMed] [Google Scholar]
  19. Weetman A. P., Volkman D. J., Burman K. D., Margolick J. B., Petrick P., Weintraub B. D., Fauci A. S. The production and characterization of thyroid-derived T-cell lines in Graves' disease and Hashimoto's thyroiditis. Clin Immunol Immunopathol. 1986 Apr;39(1):139–150. doi: 10.1016/0090-1229(86)90213-8. [DOI] [PubMed] [Google Scholar]
  20. Yssel H., De Vries J. E., Koken M., Van Blitterswijk W., Spits H. Serum-free medium for generation and propagation of functional human cytotoxic and helper T cell clones. J Immunol Methods. 1984 Aug 3;72(1):219–227. doi: 10.1016/0022-1759(84)90450-2. [DOI] [PubMed] [Google Scholar]
  21. Zinkernagel R. M., Callahan G. N., Althage A., Cooper S., Klein P. A., Klein J. On the thymus in the differentiation of "H-2 self-recognition" by T cells: evidence for dual recognition? J Exp Med. 1978 Mar 1;147(3):882–896. doi: 10.1084/jem.147.3.882. [DOI] [PMC free article] [PubMed] [Google Scholar]

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