Modulation of Graft-versus-Host (GvH) Disease in the Rat; Effect of Hydroxyurea on the Mixed Lymphocyte Reaction and Graft-versus-Host Reactivity

  • Robert Peter Gale
  • Caprice Rutkosky
  • David W. Golde


The graft-versus-host (GvH) reaction is a complex biologic phenomenon, the underlying cellular events of which are not fully defined (for reviews, see refs. 8 and 14). Studies in congenic mice indicate an important relationship between the Ir region of the H-2 gene complex and GvH reactivity (9, 18, 20). Because Ir gene products are known to influence lymphocyte recognition and proliferation in the mixed lymphocyte reaction (MLR) (1, 2, 19), it has been suggested that GvH and MLR genes are identical (18, 25). There are considerable data to support this concept as well as data to suggest an important role for non-MLR and non-Ir region genes in initiating GvH disease. Isolated K-region and possibly D-region differences can produce a weak GvH reaction (18) as can non-H-2 loci (5, 10). Demonstration of GvH reactivity of non-Ir region loci depends on the assay employed and frequently occurs in the absence of a detectable MLR or the generation of cytotoxic lymphocytes. GvH disease frequently develops in dogs and primates grafted with MLR nonreactive allogeneic bone marrow (7, 27, 28) without acquisition of MLR reactivity (22). Finally, there are preliminary data, which suggest that GvH and MLR reactive cells represent separate T-lymphocyte subpopulations expressing quantitative differences in Thy-1 antigen and in Ly alleles (15, 17).


Stimulator Cell Stimulation Index Mixed Lymphocyte Reaction Popliteal Lymph Node Phoid Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. (1).
    Bach, F. H., Bach, M. L., and Klein, J. Genetic and immunological complexity of major histocompatibility regions. Sciences, 176:1024, 1972.Google Scholar
  2. (2).
    Bach, F. H., Widmer, M. B., Bach, M. L., and Klein, J. Serologically defined and lymphocyte-defined components of the major histocompatibility complex in the mouse. J. Exp. Med., 136: 1430, 1972.PubMedCrossRefGoogle Scholar
  3. (3).
    Cantor, H., and Asofsky, R. Synergy among lymphoid cells mediating the graft-versus-host response. J. Exp. Med., 131:235, 1970.Google Scholar
  4. (4).
    Cantor, H., and Asofsky, R. Synergy among lymphoid cells mediating the graft-versus-host response. J. Exp. Med., 135:764, 1972.Google Scholar
  5. (5).
    Cantrell, J. L., and Hildemann, W. H. Characteristics of disparate histocompatibility barriers in congenic strains of mice. Transplantation, 14:761,1972.Google Scholar
  6. (6).
    Canty, T. G., and Wunderlich, J. R. Quantitative in vitro assay of cytotoxic cellular immunity. J. Natl. Cancer Inst., 45: 761, 1970.PubMedGoogle Scholar
  7. (7).
    Cline, M. J., Gale, R. P., and Stiehm, E. R. Bone marrow transplantation in man. Ann. Int. Med., 83: 691, 1975.CrossRefGoogle Scholar
  8. (8).
    Elkins, W. L. Cellular immunology and the pathogenesis of graft versus host reactions. Prog. Allergy, 15: 78, 1971.PubMedCrossRefGoogle Scholar
  9. (9).
    Elkins, W. L., Kavathas, P., and Bach, F. H. Activation of T cells by H-2 factors in the graft-vs-host reaction. Transplant. Proc., 5:1759, 1973.Google Scholar
  10. (10).
    Festenstein, H., Abbasi, K., Sachs, J. A., and Oliver, R. T. D. Serologically undetectable immune responses in transplantation. Transplant. Proc., 4: 219, 1972.PubMedGoogle Scholar
  11. (11).
    Ford, W. L., Burr, W., and Simonsen, M. A lymph node weight assay for the graft-versus-host activity of rat lymphoid cells. Transplant., 10: 258, 1970.CrossRefGoogle Scholar
  12. (12).
    Golde, D. W., Bersch, M., and Cline, M. J. Potentiation of erythropoiesis in vitro by dexamethason. J. Clin. Invest., 57: 57, 1976.PubMedCrossRefGoogle Scholar
  13. (13).
    Golde, D. W., and Cline, M. J. Identification of the colony-stimulating cell in human peripheral blood. J. Clin. Invest., 51:2981, 1972.Google Scholar
  14. (14).
    Grebe, S. C., and Streilein, J. W. Graft-versus-host reactions: A review. Adv. Immunol., 22: 119, 1976.PubMedCrossRefGoogle Scholar
  15. (15).
    Howe, M. L., and Cohen, L. Participation of lymphoid cell subpopulations in the mixed lymphocyte interaction, Lindahl-Kiessling, L. and Osoba, D., eds. In Proc. 8th Leukocyte Culture Conf., p. 611. New York: Academic Press, 1974.Google Scholar
  16. (16).
    Iscove, N. N., Senn, J. S., Till, J. E., and McCulloch, E. A. Colony formation by normal and leukemic human marrow cells in culture: Effect of conditioned medium from human leukocytes. Blood, 37:1, 1971.Google Scholar
  17. (17).
    Kisielow, P., Hirst, J. A., Shiku, H., Beverley, P. C. L., Hoffmann, M. K., Boyse, E. A., and Oettgen, H. F. Ly antigens as markers for functionally distinct subpopulation of thymus-derived lymphocytes of the mouse. Nature (London), 253: 219, 1975.CrossRefGoogle Scholar
  18. (18).
    Klein, J., and Park, J. M. Graft-versus-host reaction across different regions of the H-2 complex of the mouse. J. Exp. Med., 13:1213, 1973.Google Scholar
  19. (19).
    Klein, J., Widmer, M. B., Segall, M., and Bach, F. H. Mixed lymphocyte culture reactivity and H-2 histocompatibility loci differences. Cell Immunol., 4: 442, 1972.PubMedCrossRefGoogle Scholar
  20. (20).
    Livnat, S., Klein, J., and Bach, F. H. Graft-versushost reaction in strains of mice identical for H-2K and H-2D antigens. Nature [New Biol.], 243:42,1973.Google Scholar
  21. (21).
    Metcalf, D. Effect of thymidine suiciding on colony formation in vitro by mouse hematopoietic cells. Proc. Soc. Exp. Biol. Med., 139: 511, 1972.PubMedGoogle Scholar
  22. (22).
    Opelz, G., Gale, R. P., and the UCLA Bone Marrow Transplant Team. Absence of specific mixed leukocyte culture reactivity during graft-versushost disease ad following bone marrow transplant rejection. Transplantation, 22: 474, 1976.PubMedCrossRefGoogle Scholar
  23. (23).
    Parker, J. W., and Metcalf, D. Production of colony-stimulating factor in mixed leukocyte cultures. Immunology, 26:1039, 1974.Google Scholar
  24. (24).
    Rich, R. R., Kirkpatrick, C. H., and Smith, T. K. Simultaneous suppression of responses to allogeneic tissue in vitro and in vivo. Cell Immunol., 5: 190, 1972.CrossRefGoogle Scholar
  25. (25).
    Rodey, G. E., Bortin, M. M., Bach, F. H., and Rimm, A. A. Mixed leukocyte culture reactivity and. chronic graft-versus-host reaction (secondary disease) between allogenic H-2k mouse strains. Transplantation, 17: 84, 1974.PubMedCrossRefGoogle Scholar
  26. (26).
    Salmon, S. E., Krakaner, R. S., and Whitmore, W. F. Lymphocyte stimulation: selective destruction of cells during blastogenic response to transplantation antigens. Science, 1 72: 490, 1971.CrossRefGoogle Scholar
  27. (27).
    Storb, R., Welden, P. L., Schroeder, M. L., Graham, T. C., Lerner, K. G., and Thomas, E. D. Marrow grafts between canine littermates homozygous for lymphocyte defined histocompatibility antigens. Transplantation, 21:299, 1976.Google Scholar
  28. (28).
    Thomas, E. D., Storb, R., Clift, R. A., Feber, A., Johnson, F. L., Neiman, P. E., Lerner, K. G., Glucksberg, H., and Buckner, C. D. Bone marrow transplantation. New Engl. J. Med., 292: Part I, 832; and Part II, 895; 1975.Google Scholar
  29. (29).
    Tigelaar, R. E., and Asofsky, R. Synergy among lymphoid cells mediating the graft-versus-host response. J. Exp. Med., 135:1059, 1972.Google Scholar
  30. (30).
    Tigelaar, R. E., and Asofsky, R. Synergy among lymphoid cells mediating the graft-versus-host response. J. Exp. Med., 137:239, 1973.Google Scholar
  31. (31).
    Zosche, D. C., and Bach, F. H. Specifity of antigen recognition of human lymphocytes in vitro. Science, 170:1404, 1970.Google Scholar

Copyright information

© Springer Science+Business Media New York 1977

Authors and Affiliations

  • Robert Peter Gale
  • Caprice Rutkosky
  • David W. Golde

There are no affiliations available

Personalised recommendations