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. 1988 Mar;63(3):373–381.

Investigation of the mechanism of active enhancement of renal allograft survival by blood transfusion.

R L Quigley 1, K J Wood 1, P J Morris 1
PMCID: PMC1454746  PMID: 2965097

Abstract

Transfusion with donor blood before transplantation can prolong the survival of renal allografts in the rat. The phenomenon is donor specific. We have investigated the effect of blood transfusion on both lymphocyte proliferation and the generation of donor-specific cytotoxic cells. In the first instance the kinetics of the proliferative responses of lymph node, spleen and thoracic duct lymph (TDL) leucocytes (harvested 7 days after transfusion of donor-specific blood, third-party allogeneic blood, syngeneic blood or no treatment) to lymph node stimulator cells were determined in a one-way mixed lymphocyte culture (MLC). Four strain combinations (LEW to DA, LEW to PVG, PVG to DA and DA to PVG) were investigated in this study. Maximal proliferation was observed at 4 days in the MLC and this was not altered by prior blood transfusion. When lymph node and TDL cells from transfused recipients were used as responders and stimulation was provided by cells from the same strain of rat as the blood donor, there was a significant depression of the MLC response compared to the response of cells harvested from untreated animals or animals given a syngeneic blood transfusion. This correlated with the behaviour of renal allografts in the same strain combinations. Lymph node and TDL cells harvested from rats that had received a third-party blood transfusion produced variable results in the MLC, ranging from a normal to a depressed response. No prolongation of allograft survival was noted in any animals pretreated with third-party blood. In contrast, when spleen cells were used as responder cells there was a donor-specific increase in the proliferative response on Day 4 in all strain combinations tested. In the second instance, specific cytotoxic activity was generated by in vitro (MLC) stimulation of lymph node or TDL, but not spleen, cell responders harvested from transfused or untreated rats. The activity of cytotoxic cells generated in MLC was quantified in a 51Cr-release assay, using Con A blast lymph node target cells prepared from animals of the same strain as the blood donor or a third-party strain. The specific cytotoxic activity generated was significantly increased when the responding cells were harvested from an animal that had received a donor-specific transfusion and then been restimulated by the blood donor in MLC.(ABSTRACT TRUNCATED AT 400 WORDS)

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Selected References

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  1. Bach F. H., Segall M., Zier K. S., Sondel P. M., Alter B. J., Bach M. L. Cell mediated immunity: separation of cells involved in recognitive and destructive phases. Science. 1973 Apr 27;180(4084):403–406. doi: 10.1126/science.180.4084.403. [DOI] [PubMed] [Google Scholar]
  2. Bernstein I. D., Wright P. W. Generation of cytotoxic lymphocytes in mixed leukocyte culture by rat lymphoid cells. Transplantation. 1976 Feb;21(2):173–178. [PubMed] [Google Scholar]
  3. Cantor H., Boyse E. A. Functional subclasses of T lymphocytes bearing different Ly antigens. II. Cooperation between subclasses of Ly+ cells in the generation of killer activity. J Exp Med. 1975 Jun 1;141(6):1390–1399. doi: 10.1084/jem.141.6.1390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dallman M. J., Mason D. W., Webb M. The roles of host and donor cells in the rejection of skin allografts by T cell-deprived rats injected with syngeneic T cells. Eur J Immunol. 1982 Jun;12(6):511–518. doi: 10.1002/eji.1830120612. [DOI] [PubMed] [Google Scholar]
  5. Dallman M. J., Wood K. J., Morris P. J. Specific cytotoxic T cells are found in the nonrejected kidneys of blood-transfused rats. J Exp Med. 1987 Feb 1;165(2):566–571. doi: 10.1084/jem.165.2.566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fabre J. W., Morris P. J. The effect of donor strain blood pretreatment on renal allograft rejection in rats. Transplantation. 1972 Nov;14(5):608–617. doi: 10.1097/00007890-197211000-00013. [DOI] [PubMed] [Google Scholar]
  7. Fabre J. W., Morris P. J. The mechanism of specific immunosuppression of renal allograft rejection by donor strain blood. Transplantation. 1972 Nov;14(5):634–640. doi: 10.1097/00007890-197211000-00016. [DOI] [PubMed] [Google Scholar]
  8. Fabre J., Lim S. H., Morris P. J. Renal transplantation in the rat: details of a technique. Aust N Z J Surg. 1971 Aug;41(1):69–75. [PubMed] [Google Scholar]
  9. GOWANS J. L., KNIGHT E. J. THE ROUTE OF RE-CIRCULATION OF LYMPHOCYTES IN THE RAT. Proc R Soc Lond B Biol Sci. 1964 Jan 14;159:257–282. doi: 10.1098/rspb.1964.0001. [DOI] [PubMed] [Google Scholar]
  10. Hutchinson I. V., Morris P. J. The role of major and minor histocompatibility antigens in active enhancement of rat kidney allograft survival by blood transfusion. Transplantation. 1986 Feb;41(2):166–170. doi: 10.1097/00007890-198602000-00006. [DOI] [PubMed] [Google Scholar]
  11. Häyry P., Soots A., von Willebrand E., Wiktorowicz K. Composition, subclass distribution, and preliminary analysis of the functions of host inflammatory cells infiltrating renal allografts during rejection. Transplant Proc. 1979 Mar;11(1):785–789. [PubMed] [Google Scholar]
  12. Ludwin D., Joseph S., Singal D. P. MLC-inhibiting antibodies in mice after blood transfusions. Transplantation. 1986 Jan;41(1):100–104. doi: 10.1097/00007890-198601000-00020. [DOI] [PubMed] [Google Scholar]
  13. MacDonald H. R., Lees R. K. Dissociation of differentiation and proliferation in the primary induction of cytolytic T lymphocytes by alloantigens. J Immunol. 1980 Mar;124(3):1308–1313. [PubMed] [Google Scholar]
  14. Maki T., Gottschalk R., Wood M. L., Monaco A. P. Specific unresponsiveness to skin allografts in anti-lymphocyte serum-treated, marrow-injected mice: participation of donor marrow-derived suppressor T cells. J Immunol. 1981 Oct;127(4):1433–1438. [PubMed] [Google Scholar]
  15. Mason D. W., Dallman M. J., Arthur R. P., Morris P. J. Mechanisms of allograft rejection: the roles of cytotoxic T-cells and delayed-type hypersensitivity. Immunol Rev. 1984;77:167–184. doi: 10.1111/j.1600-065x.1984.tb00721.x. [DOI] [PubMed] [Google Scholar]
  16. Nagarkatti P. S., Singal D. P. Blood-transfusion-induced suppression of cytotoxic T lymphocyte responses in mice. Transplantation. 1983 Nov;36(5):520–525. doi: 10.1097/00007890-198311000-00010. [DOI] [PubMed] [Google Scholar]
  17. Opelz G., Terasaki P. I. Improvement of kidney-graft survival with increased numbers of blood transfusions. N Engl J Med. 1978 Oct 12;299(15):799–803. doi: 10.1056/NEJM197810122991503. [DOI] [PubMed] [Google Scholar]
  18. Salvatierra O., Jr, Vincenti F., Amend W., Potter D., Iwaki Y., Opelz G., Terasaki P., Duca R., Cochrum K., Hanes D. Deliberate donor-specific blood transfusions prior to living related renal transplantation. A new approach. Ann Surg. 1980;192(4):543–552. doi: 10.1097/00000658-198010000-00012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sprent J., Miller J. F. Effect of recent antigen priming on adoptive immune responses. II. Specific unresponsiveness of circulating lymphocytes from mice primed with heterologous erythrocytes. J Exp Med. 1974 Jan 1;139(1):1–12. doi: 10.1084/jem.139.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wagner H., Röllinghoff M. Secondary cytotoxic allograft responses in vitro. II. Differentiation of memory T cells into cytotoxic T lymphocytes in the absence of cell proliferation. Eur J Immunol. 1976 Jan;6(1):15–21. doi: 10.1002/eji.1830060105. [DOI] [PubMed] [Google Scholar]
  21. Webb M., Mason D. W., Williams A. F. Inhibition of mixed lymphocyte response by monoclonal antibody specific for a rat T lymphocyte subset. Nature. 1979 Dec 20;282(5741):841–843. doi: 10.1038/282841a0. [DOI] [PubMed] [Google Scholar]
  22. Weiss A., Fitch F. W. Macrophages suppress CTL generation in rat mixed leukocyte cultures. J Immunol. 1977 Aug;119(2):510–516. [PubMed] [Google Scholar]
  23. Wood K. J., Dallman M. J., Morris P. J. Blood transfusion induces specific cytotoxic cells. Transplant Proc. 1987 Feb;19(1 Pt 2):1458–1460. [PubMed] [Google Scholar]
  24. Wood M. L., Gottschalk R., Monaco A. P. Comparison of immune responsiveness in mice after single or multiple donor-specific transfusions. J Immunol. 1984 Feb;132(2):651–655. [PubMed] [Google Scholar]
  25. Wood M. L., Gottschalk R., Monaco A. P. Immune reactivity in congenic mice after allogeneic or isogeneic transfusion. Transplantation. 1986 Apr;41(4):489–494. doi: 10.1097/00007890-198604000-00015. [DOI] [PubMed] [Google Scholar]

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