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. 1983 May;71(5):1322–1330. doi: 10.1172/JCI110883

Factors affecting the autologous mixed lymphocyte reaction in kidney transplantation.

L Fuller, C Flaa, D Jaffe, J Strauss, G K Kyriakides, J Miller
PMCID: PMC436994  PMID: 6222068

Abstract

In long-term well adapted kidney transplant recipients we have found a close correlation between the T helper (TH):T suppressor/cytotoxic (TS/C) subset ratios and the presence of T cells that respond in the autologous mixed lymphocyte reaction (AMLR). In 21 recipients with T cell E rosette levels ranging between 53 and 86% and TH:TS/C ratios between 0.15 to 2.10, ratios of greater than 0.8 correlated with AMLR responses (13/13), and ratios of less than 0.8 with AMLR nonreactivity (7/7). By contrast, the allogeneic MLR showed no apparent correlation with the TH:TS/C ratios or with the AMLR pre- or postoperatively. It was found that the AMLR in 22 of 23 normal individuals was markedly inhibited by autologous T cells obtained from peripheral blood lymphocytes, exposed to 3,000 rad (Tx) and added as a third component to the cultures. In contrast, 13 of 13 kidney transplant recipients failed to exhibit this Tx AMLR inhibitory cell population. The "naturally occurring" T inhibitory cells, fractionated by an affinity column chromatography procedure into x-irradiated TH and TS/C subsets, inhibited the AMLR to the same extent as unseparated Tx cells. In cell interchange studies performed in four of five HLA identical donor-recipient pairs the Tx cells of the (normal) donor inhibited the recipient AMLR (immunosuppressed), but recipient Tx cells failed to inhibit the donor AMLR. Finally T cells, primed in AMLR and allogeneic MLR for 10 d were tested for AMLR or allogeneic MLR inhibitory activity. Allogeneic MLR primed x-irradiated cells, inhibited both the AMLR and allogeneic MLR while AMLR x-irradiated primed cells inhibited neither reaction. The Tx AMLR inhibitor found in normal peripheral blood, appears to be a cell that is highly sensitive to the effects of biologic or pharmacologic immunosuppressive agents.

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Selected References

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

  1. Evans R. L., Lazarus H., Penta A. C., Schlossman S. F. Two functionally distinct subpopulations of human T cells that collaborate in the generation of cytotoxic cells responsible for cell-mediated lympholysis. J Immunol. 1978 Apr;120(4):1423–1428. [PubMed] [Google Scholar]
  2. Fournier C., Charreire J. Autologous mixed lymphocyte reaction in man. II. Autoreactive and alloreactive cells belong to two different T cell subsets. J Immunol. 1982 Jun;128(6):2698–2703. [PubMed] [Google Scholar]
  3. Gershon R. K., Eardley D. D., Durum S., Green D. R., Shen F. W., Yamauchi K., Cantor H., Murphy D. B. Contrasuppression. A novel immunoregulatory activity. J Exp Med. 1981 Jun 1;153(6):1533–1546. doi: 10.1084/jem.153.6.1533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hahn B. H., MacDermott R. P., Jacobs S. B., Pletscher L. S., Beale M. G. Immunosuppressive effects of low doses of glucocorticoids: effects on autologous and allogeneic mixed leukocyte reactions. J Immunol. 1980 Jun;124(6):2812–2817. [PubMed] [Google Scholar]
  5. Hattler B. G., Jr, Karesh C., Miller J. Inhibition of the mixed lymphocyte culture response by antibody following successful human renal transplantation. Tissue Antigens. 1971;1(6):270–275. doi: 10.1111/j.1399-0039.1971.tb00105.x. [DOI] [PubMed] [Google Scholar]
  6. Hattler B. G., Jr, Miller J., Johnson M. C. Cellular and humoral factors governing canine mixed lymphocyte cultures after renal transplantation. II. Cellular. Transplantation. 1972 Jul;14(1):47–56. doi: 10.1097/00007890-197207000-00007. [DOI] [PubMed] [Google Scholar]
  7. Jerne N. K. Towards a network theory of the immune system. Ann Immunol (Paris) 1974 Jan;125C(1-2):373–389. [PubMed] [Google Scholar]
  8. Kadish A. S., Tansey F. A., Yu G. S., Doyle A. T., Bloom B. R. Interferon as a mediator of human lymphocyte suppression. J Exp Med. 1980 Mar 1;151(3):637–650. doi: 10.1084/jem.151.3.637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kozak R. W., Moody C. E., Staiano-Coico L., Weksler M. E. Lymphocyte transformation induced by autologous cells. XII. Quantitative and qualitative differences between human autologous and allogeneic reactive T lymphocytes. J Immunol. 1982 Apr;128(4):1723–1727. [PubMed] [Google Scholar]
  10. Kuntz M. M., Innes J. B., Weksler M. E. Lymphocyte transformation induced by autologous cells. IV. Human T-lymphocyte proliferation induced by autologous or allogeneic non-T lymphocytes. J Exp Med. 1976 May 1;143(5):1042–1054. doi: 10.1084/jem.143.5.1042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kuntz M. M., Innes J. B., Weksler M. E. The cellular basis of the impaired autologous mixed lymphocyte reaction in patients with systemic lupus erythematosus. J Clin Invest. 1979 Jan;63(1):151–153. doi: 10.1172/JCI109270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kyriakides G. K., Severyn W., Fuller L., Esquenazi V., Flaa C., Olson L., Miller J. Effects of histocompatibility testing versus immunoreactive predisposition on kidney transplant survival. Surgery. 1982 Aug;92(2):354–361. [PubMed] [Google Scholar]
  13. MacDermott R. P., Stacey M. C. Further characterization of the human autologous mixed leukocyte reaction (MLR). J Immunol. 1981 Feb;126(2):729–734. [PubMed] [Google Scholar]
  14. Miller J., Clark C., Flaa C. In vitro generation of suppressor cells in human mixed leukocyte culture: a potential treatment modality in organ transplantation. Transplant Proc. 1979 Mar;11(1):899–903. [PubMed] [Google Scholar]
  15. Miller J., Lifton J., DeWolf W. C., Stevens B. J., Wilcox C. Efficacy of immunologic monitoring after renal transplantation. Transplant Proc. 1977 Mar;9(1):59–64. [PubMed] [Google Scholar]
  16. Miller J., Lifton J., Rood F., Hattler B. G., Jr Blocking versus cytotoxic antibody in HL-A- and mixed lymphocyte culture-identical and nonidentical human renal transplant recipients. Transplantation. 1975 Jul;20(1):53–62. doi: 10.1097/00007890-197507000-00009. [DOI] [PubMed] [Google Scholar]
  17. Moretta L., Webb S. R., Grossi C. E., Lydyard P. M., Cooper M. D. Functional analysis of two human T-cell subpopulations: help and suppression of B-cell responses by T cells bearing receptors for IgM or IgG. J Exp Med. 1977 Jul 1;146(1):184–200. doi: 10.1084/jem.146.1.184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. O'Malley J. A., Nussbaum-Blumenson A., Sheedy D., Grossmayer B. J., Ozer H. Identification of the T cell subset that produces human gamma interferon. J Immunol. 1982 Jun;128(6):2522–2526. [PubMed] [Google Scholar]
  19. Opelz G., Kiuchi M., Takasugi M., Terasaki P. I. Autologous stimulation of human lymphocyte subpopulation. J Exp Med. 1975 Nov 1;142(5):1327–1333. doi: 10.1084/jem.142.5.1327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. A monoclonal antibody reactive with the human cytotoxic/suppressor T cell subset previously defined by a heteroantiserum termed TH2. J Immunol. 1980 Mar;124(3):1301–1307. [PubMed] [Google Scholar]
  21. Sakane T., Green I. Specificity and suppressor function of human T cells responsive to autologous non-T cells. J Immunol. 1979 Aug;123(2):584–589. [PubMed] [Google Scholar]
  22. Sakane T., Steinberg A. D., Green I. Failure of autologous mixed lymphocyte reactions between T and non-T cells in patients with systemic lupus erythematosus. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3464–3468. doi: 10.1073/pnas.75.7.3464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Severyn W., Kyriakides G., Fuller L., Esquenazi V., Flaa C., Olson L., Goldsmith C., Miller J. Kidney transplantation by use of splenectomy and transfusions, cadaver haplotype matching, suppressor cell assays, and T-cell monitoring. Surgery. 1981 Aug;90(2):364–375. [PubMed] [Google Scholar]
  24. Smith J. B., Knowlton R. P. Activation of suppressor T cells in human autologous mixed lymphocyte culture. J Immunol. 1979 Jul;123(1):419–422. [PubMed] [Google Scholar]
  25. Solliday S., Bach F. H. Cytotoxicity: specificity after in vitro sensitization. Science. 1970 Dec 25;170(3965):1406–1409. doi: 10.1126/science.170.3965.1406. [DOI] [PubMed] [Google Scholar]
  26. Strom T. B., Tilney N. L., Carpenter C. B., Busch G. J. Identity and cytotoxic capacity of cells infiltrating renal allografts. N Engl J Med. 1975 Jun 12;292(24):1257–1263. doi: 10.1056/NEJM197506122922402. [DOI] [PubMed] [Google Scholar]
  27. Tomonari K. Cytotoxic T cells generated in the autologous mixed lymphocyte reaction. I. Primary autologous mixed lymphocyte reaction. J Immunol. 1980 Mar;124(3):1111–1121. [PubMed] [Google Scholar]
  28. Urbain J., Wuilmart C., Cazenave P. A. Idiotypic regulation in immune networks. Contemp Top Mol Immunol. 1981;8:113–148. doi: 10.1007/978-1-4684-3917-5_4. [DOI] [PubMed] [Google Scholar]
  29. Weksler M. E., Kozak R. Lymphocyte transformation induced by autologous cells. V. Generation of immunologic memory and specificity during the autologous mixed lymphocyte reaction. J Exp Med. 1977 Dec 1;146(6):1833–1838. doi: 10.1084/jem.146.6.1833. [DOI] [PMC free article] [PubMed] [Google Scholar]

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