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. 1992 Aug 1;176(2):407–413. doi: 10.1084/jem.176.2.407

Correlation between lymphocyte-induced donor-specific tolerance and donor cell recirculation

PMCID: PMC2119335  PMID: 1500853

Abstract

Intravenous infusion of mice with major histocompatibility complex (MHC) incompatible lymphocytes can inhibit the response of recipient T cells capable of recognizing the injected cells, and can enhance survival of grafts sharing MHC with the injected cells. However, neither T cell inactivation nor graft survival enhancement is always achieved. This is particularly true for donor cells that are fully allogeneic (as compared to semiallogeneic) to the recipient. We show here that both donor-specific induced response reduction and graft survival enhancement are directly correlated with the ability of the injected lymphoid cells to persist in the recirculating lymphocyte pool of the host. Whether donor cells persist correlates inversely with the level of natural killer cell (NK) activity in the host. Fully allogeneic cells can only persist in hosts with low NK activity and can then induce response reduction. Both persistence and response reduction are abrogated by injection of the host with poly-I:C, a treatment that boosts host NK activity. The same treatment also destroys the ability of semiallogeneic injected cells to persist, to induce response reduction, and to enhance skin graft survival.

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Selected References

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  1. Carlson G. A., Wegmann T. G. Rapid in vivo destruction of semi-syngeneic and allogeneic cells by nonimmunized mice as a consequence of nonidentity at H-2. J Immunol. 1977 Jun;118(6):2130–2137. [PubMed] [Google Scholar]
  2. Djeu J. Y., Heinbaugh J. A., Holden H. T., Herberman R. B. Role of macrophages in the augementation of mouse natural killer cell activity by poly I:C and interferon. J Immunol. 1979 Jan;122(1):182–188. [PubMed] [Google Scholar]
  3. Fink P. J., Shimonkevitz R. P., Bevan M. J. Veto cells. Annu Rev Immunol. 1988;6:115–137. doi: 10.1146/annurev.iy.06.040188.000555. [DOI] [PubMed] [Google Scholar]
  4. Heeg K., Wagner H. Induction of peripheral tolerance to class I major histocompatibility complex (MHC) alloantigens in adult mice: transfused class I MHC-incompatible splenocytes veto clonal responses of antigen-reactive Lyt-2+ T cells. J Exp Med. 1990 Sep 1;172(3):719–728. doi: 10.1084/jem.172.3.719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Herberman R. B., Holden H. T. Natural cell-mediated immunity. Adv Cancer Res. 1978;27:305–377. doi: 10.1016/s0065-230x(08)60936-7. [DOI] [PubMed] [Google Scholar]
  6. Heslop B. F., McNeilage L. J. The F1 hybrid effect in allogeneic lymphocyte cytotoxicity. Points of similarity between hybrid resistance and ALC. Transplantation. 1989 Oct;48(4):634–639. [PubMed] [Google Scholar]
  7. Hori S., Sato S., Kitagawa S., Azuma T., Kokudo S., Hamaoka T., Fujiwara H. Tolerance induction of allo-class II H-2 antigen-reactive L3T4+ helper T cells and prolonged survival of the corresponding class II H-2-disparate skin graft. J Immunol. 1989 Sep 1;143(5):1447–1452. [PubMed] [Google Scholar]
  8. Höglund P., Glas R., Ohlén C., Ljunggren H. G., Kärre K. Alteration of the natural killer repertoire in H-2 transgenic mice: specificity of rapid lymphoma cell clearance determined by the H-2 phenotype of the target. J Exp Med. 1991 Aug 1;174(2):327–334. doi: 10.1084/jem.174.2.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Höglund P., Ljunggren H. G., Ohlén C., Ahrlund-Richter L., Scangos G., Bieberich C., Jay G., Klein G., Kärre K. Natural resistance against lymphoma grafts conveyed by H-2Dd transgene to C57BL mice. J Exp Med. 1988 Oct 1;168(4):1469–1474. doi: 10.1084/jem.168.4.1469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ishikawa H., Hino T., Kato H., Suzuki H., Saito K. Cytotoxic T lymphocyte response to minor H-42a alloantigen in H-42b mice: clonal inactivation of the precursor cytotoxic T lymphocytes by veto-like spleen cells that express the H-42a antigen. J Immunol. 1986 Oct 1;137(7):2080–2088. [PubMed] [Google Scholar]
  11. Kasai M., Yoneda T., Habu S., Maruyama Y., Okumura K., Tokunaga T. In vivo effect of anti-asialo GM1 antibody on natural killer activity. Nature. 1981 May 28;291(5813):334–335. doi: 10.1038/291334a0. [DOI] [PubMed] [Google Scholar]
  12. Kasaian M. T., Biron C. A. The activation of IL-2 transcription in L3T4+ and Lyt-2+ lymphocytes during virus infection in vivo. J Immunol. 1989 Feb 15;142(4):1287–1292. [PubMed] [Google Scholar]
  13. Kast W. M., Van Twuyver E., Mooijaart R. J., Verveld M., Kamphuis A. G., Melief C. J., De Waal L. P. Mechanism of skin allograft enhancement across an H-2 class I mutant difference. Evidence for involvement of veto cells. Eur J Immunol. 1988 Dec;18(12):2105–2108. doi: 10.1002/eji.1830181238. [DOI] [PubMed] [Google Scholar]
  14. Kitagawa S., Iwata H., Sato S., Shimizu J., Hamaoka T., Fujiwara H. Heterogenous graft rejection pathways in class I major histocompatibility complex-disparate combinations and their differential susceptibility to immunomodulation induced by intravenous presensitization with relevant alloantigens. J Exp Med. 1991 Sep 1;174(3):571–581. doi: 10.1084/jem.174.3.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kiziroglu F., Miller R. G. In vivo functional clonal deletion of recipient CD4+ T helper precursor cells that can recognize class II MHC on injected donor lymphoid cells. J Immunol. 1991 Feb 15;146(4):1104–1112. [PubMed] [Google Scholar]
  16. Kärre K., Ljunggren H. G., Piontek G., Kiessling R. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature. 1986 Feb 20;319(6055):675–678. doi: 10.1038/319675a0. [DOI] [PubMed] [Google Scholar]
  17. Lagaaij E. L., Hennemann I. P., Ruigrok M., de Haan M. W., Persijn G. G., Termijtelen A., Hendricks G. F., Weimar W., Claas F. H., van Rood J. J. Effect of one-HLA-DR-antigen-matched and completely HLA-DR-mismatched blood transfusions on survival of heart and kidney allografts. N Engl J Med. 1989 Sep 14;321(11):701–705. doi: 10.1056/NEJM198909143211101. [DOI] [PubMed] [Google Scholar]
  18. Ljunggren H. G., Kärre K. In search of the 'missing self': MHC molecules and NK cell recognition. Immunol Today. 1990 Jul;11(7):237–244. doi: 10.1016/0167-5699(90)90097-s. [DOI] [PubMed] [Google Scholar]
  19. Martin D. R., Miller R. G. In vivo administration of histoincompatible lymphocytes leads to rapid functional deletion of cytotoxic T lymphocyte precursors. J Exp Med. 1989 Sep 1;170(3):679–690. doi: 10.1084/jem.170.3.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Miller R. G. An immunological suppressor cell inactivating cytotoxic T-lymphocyte precursor cells recognizing it. Nature. 1980 Oct 9;287(5782):544–546. doi: 10.1038/287544a0. [DOI] [PubMed] [Google Scholar]
  21. Miller R. G., Muraoka S., Claesson M. H., Reimann J., Benveniste P. The veto phenomenon in T-cell regulation. Ann N Y Acad Sci. 1988;532:170–176. doi: 10.1111/j.1749-6632.1988.tb36336.x. [DOI] [PubMed] [Google Scholar]
  22. Miller R. G., Phillips R. A. Reduction of the in vitro cytotoxic lymphocyte response produced by in vivo exposure to semiallogeneic cells: recruitment or active suppression? J Immunol. 1976 Nov;117(5 PT2):1913–1921. [PubMed] [Google Scholar]
  23. Opelz G., Mickey M. R., Terasaki P. I. Blood transfusions and kidney transplants: remaining controversies. Transplant Proc. 1981 Mar;13(1 Pt 1):136–141. [PubMed] [Google Scholar]
  24. Rammensee H. G., Fink P. J., Bevan M. J. Functional clonal deletion of class I-specific cytotoxic T lymphocytes by veto cells that express antigen. J Immunol. 1984 Nov;133(5):2390–2396. [PubMed] [Google Scholar]
  25. Rammensee H. G., Hügin D. Masking of veto function in vivo by activated CD4+ T lymphocytes. Eur J Immunol. 1989 Apr;19(4):643–648. doi: 10.1002/eji.1830190411. [DOI] [PubMed] [Google Scholar]
  26. Roder J. C. The beige mutation in the mouse. I. A stem cell predetermined impairment in natural killer cell function. J Immunol. 1979 Nov;123(5):2168–2173. [PubMed] [Google Scholar]
  27. Rolstad B., Fossum S. Allogeneic lymphocyte cytotoxicity (ALC) in rats: establishment of an in vitro assay, and direct evidence that cells with natural killer (NK) activity are involved in ALC. Immunology. 1987 Feb;60(2):151–157. [PMC free article] [PubMed] [Google Scholar]
  28. Singal D. P., Ludwin D., Blajchman M. A. Blood transfusion and renal transplantation. Br J Haematol. 1985 Dec;61(4):595–602. doi: 10.1111/j.1365-2141.1985.tb02872.x. [DOI] [PubMed] [Google Scholar]
  29. Snell G. D. Recognition structures determined by the H-2 complex. Transplant Proc. 1976 Jun;8(2):147–156. [PubMed] [Google Scholar]
  30. Wilson D. B., Nowell P. C. Quantitative studies on the mixed lymphocyte interaction in rats. V. Tempo and specificity of the proliferative response and the number of reactive cells from immunized donors. J Exp Med. 1971 Mar 1;133(3):442–453. doi: 10.1084/jem.133.3.442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. van Twuyver E., Kast W. M., Mooijaart R. J., Melief C. J., De Waal L. P. Induction of transplantation tolerance by intravenous injection of allogeneic lymphocytes across an H-2 class II mismatch. Different mechanisms operate in tolerization across an H-2 class I vs. H-2 class II disparity. Eur J Immunol. 1990 Feb;20(2):441–444. doi: 10.1002/eji.1830200232. [DOI] [PubMed] [Google Scholar]
  32. van Twuyver E., Mooijaart R. J., ten Berge I. J., van der Horst A. R., Wilmink J. M., Kast W. M., Melief C. J., de Waal L. P. Pretransplantation blood transfusion revisited. N Engl J Med. 1991 Oct 24;325(17):1210–1213. doi: 10.1056/NEJM199110243251704. [DOI] [PubMed] [Google Scholar]

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