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. 1985 Jun 1;161(6):1483–1502. doi: 10.1084/jem.161.6.1483

Phenotype of recovering lymphoid cell populations after marrow transplantation

PMCID: PMC2187630  PMID: 3159819

Abstract

Four patients who received bone marrow transplants were studied sequentially during the posttransplant period to define the pattern of recovering lymphoid cell types. Three patients received T cell- depleted, HLA-matched marrow, and one received untreated marrow from an identical twin. Blood lymphoid cells were labeled with 25 different pairs of monoclonal antibodies. In each sample, one antibody was conjugated to fluorescein and one to phycoerythrin, thus allowing simultaneous assessment of the expression of the two markers using the fluorescence activated cell sorter. A total of 14 antibodies were used, routinely including HLE, Leu-M3, Leu-4, Leu-1, Leu-5, Leu-9, Leu-6, Leu- 2, Leu-3, HLA-DR, Leu-7, Leu-11, Leu-15, and Leu-12. Other antibodies were used to further define some populations. This study has allowed us to define six distinct cell types that have appeared in all four patients by day 90 posttransplantation, and which account for 90-100% of all circulating lymphoid cells. These cell types are (a) T helper cells expressing Leu-1, Leu-4, Leu-9, Leu-5, Leu-3, and variable amounts of HLA-DR; (b) T suppressor cells expressing Leu-1, Leu-4, Leu- 9, Leu-5, Leu-2, and variable amounts of HLA-DR; (c) B cells expressing Leu-12, B1, HLA-DR, IgD, and IgM, but none of the T cell antigens; (d) an unusual B cell phenotype (Leu-1 B) expressing all of the B cell markers, and also having low amounts of Leu-1, but none of the other T cell antigens; (e) natural killer (NK) cells expressing Leu-11, Leu-15, Leu-5 but none of the other T cell or B cell markers; (f) NK cells expressing Leu-11, Leu-15, Leu-5, and low levels of Leu-2. Both NK types also express Leu-7 on some, but not all cells. The relative frequencies of these cell types varied among the patients and with time, but the striking findings were the presence of relatively few mature T cells, large numbers of NK cells, and the preponderance of the unusual Leu-1 B cell over conventional B cells in all three patients who developed B cells. Sorting experiments confirmed the NK activity of the major NK cell phenotypes, and DNA analysis confirmed that all of the cells studied were of donor origin. In addition, analysis of Ig genes in one patient showed that the Leu-1 B cells were not clonally rearranged.(ABSTRACT TRUNCATED AT 400 WORDS)

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Selected References

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  1. Abo T., Balch C. M. A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1). J Immunol. 1981 Sep;127(3):1024–1029. [PubMed] [Google Scholar]
  2. Atkinson K., Hansen J. A., Storb R., Goehle S., Goldstein G., Thomas E. D. T-cell subpopulations identified by monoclonal antibodies after human marrow transplantation. I. Helper-inducer and cytotoxic-suppressor subsets. Blood. 1982 Jun;59(6):1292–1298. [PubMed] [Google Scholar]
  3. Ault K. A., Weiner H. L. Natural killing of measles-infected cells by human lymphocytes. J Immunol. 1979 Jun;122(6):2611–2616. [PubMed] [Google Scholar]
  4. Beverley P. C., Linch D., Delia D. Isolation of human haematopoietic progenitor cells using monoclonal antibodies. Nature. 1980 Sep 25;287(5780):332–333. doi: 10.1038/287332a0. [DOI] [PubMed] [Google Scholar]
  5. Caligaris-Cappio F., Gobbi M., Bofill M., Janossy G. Infrequent normal B lymphocytes express features of B-chronic lymphocytic leukemia. J Exp Med. 1982 Feb 1;155(2):623–628. doi: 10.1084/jem.155.2.623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chen Y. X., Evans R. L., Pollack M. S., Lanier L. L., Phillips J. H., Rousso C., Warner N. L., Brodsky F. M. Characterization and expression of the HLA-DC antigens defined by anti-Leu 10. Hum Immunol. 1984 Aug;10(4):221–235. doi: 10.1016/0198-8859(84)90088-0. [DOI] [PubMed] [Google Scholar]
  7. Clement L. T., Grossi C. E., Gartland G. L. Morphologic and phenotypic features of the subpopulation of Leu-2+ cells that suppresses B cell differentiation. J Immunol. 1984 Nov;133(5):2461–2468. [PubMed] [Google Scholar]
  8. Dimitriu-Bona A., Burmester G. R., Waters S. J., Winchester R. J. Human mononuclear phagocyte differentiation antigens. I. Patterns of antigenic expression on the surface of human monocytes and macrophages defined by monoclonal antibodies. J Immunol. 1983 Jan;130(1):145–152. [PubMed] [Google Scholar]
  9. Elfenbein G. J., Anderson P. N., Humphrey R. L., Mullins G. M., Sensenbrenner L. L., Wands J. R., Santos G. W. Immune system reconstitution following allogeneic bone marrow transplantation in man: a multiparameter analysis. Transplant Proc. 1976 Dec;8(4):641–646. [PubMed] [Google Scholar]
  10. Elfenbein G. J., Bellis M. M., Ravlin H. M., Santos G. W. Phenotypically immature B mu cells in the peripheral blood after bone marrow grafting in man. Exp Hematol. 1982 Jul;10(6):551–559. [PubMed] [Google Scholar]
  11. Friedrich W., O'Reilly R. J., Koziner B., Gebhard D. F., Jr, Good R. A., Evans R. L. T-lymphocyte reconstitution in recipients of bone marrow transplants with and without GVHD: imbalances of T-cell subpopulations having unique regulatory and cognitive functions. Blood. 1982 Apr;59(4):696–701. [PubMed] [Google Scholar]
  12. Friedrich W., O'Reilly R. J., Koziner B., Gebhard D. F., Jr, Good R. A., Evans R. L. T-lymphocyte reconstitution in recipients of bone marrow transplants with and without GVHD: imbalances of T-cell subpopulations having unique regulatory and cognitive functions. Blood. 1982 Apr;59(4):696–701. [PubMed] [Google Scholar]
  13. Fujimoto J., Levy S., Levy R. Spontaneous release of the Leu-2 (T8) molecule from human T cells. J Exp Med. 1983 Sep 1;158(3):752–766. doi: 10.1084/jem.158.3.752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gale R. P., Opelz G., Mickey M. R., Graze P. R., Saxon A. Immunodeficiency following allogeneic bone marrow transplantation. Transplant Proc. 1978 Mar;10(1):223–227. [PubMed] [Google Scholar]
  15. Gatenby P. A., Kansas G. S., Xian C. Y., Evans R. L., Engleman E. G. Dissection of immunoregulatory subpopulations of T lymphocytes within the helper and suppressor sublineages in man. J Immunol. 1982 Nov;129(5):1997–2000. [PubMed] [Google Scholar]
  16. Ginsburg D., Antin J. H., Smith B. R., Orkin S. H., Rappeport J. M. Origin of cell populations after bone marrow transplantation. Analysis using DNA sequence polymorphisms. J Clin Invest. 1985 Feb;75(2):596–603. doi: 10.1172/JCI111736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hansen J. A., Atkinson K., Martin P. J., Storb R., Longton G., Thomas E. D. Human T lymphocyte phenotypes after bone marrow transplantation. T cells expressing Ia-like antigen. Transplantation. 1983 Sep;36(3):277–281. doi: 10.1097/00007890-198309000-00010. [DOI] [PubMed] [Google Scholar]
  18. Hansson M., Beran M., Andersson B., Kiessling R. Inhibition of in vitro granulopoiesis by autologous allogeneic human NK cells. J Immunol. 1982 Jul;129(1):126–132. [PubMed] [Google Scholar]
  19. Hayakawa K., Hardy R. R., Honda M., Herzenberg L. A., Steinberg A. D., Herzenberg L. A. Ly-1 B cells: functionally distinct lymphocytes that secrete IgM autoantibodies. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2494–2498. doi: 10.1073/pnas.81.8.2494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hayakawa K., Hardy R. R., Parks D. R., Herzenberg L. A. The "Ly-1 B" cell subpopulation in normal immunodefective, and autoimmune mice. J Exp Med. 1983 Jan 1;157(1):202–218. doi: 10.1084/jem.157.1.202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Haynes B. F. Human T lymphocyte antigens as defined by monoclonal antibodies. Immunol Rev. 1981;57:127–161. doi: 10.1111/j.1600-065x.1981.tb00445.x. [DOI] [PubMed] [Google Scholar]
  22. Holmberg L. A., Miller B. A., Ault K. A. The effect of natural killer cells on the development of syngeneic hematopoietic progenitors. J Immunol. 1984 Dec;133(6):2933–2939. [PubMed] [Google Scholar]
  23. Howard F. D., Ledbetter J. A., Wong J., Bieber C. P., Stinson E. B., Herzenberg L. A. A human T lymphocyte differentiation marker defined by monoclonal antibodies that block E-rosette formation. J Immunol. 1981 Jun;126(6):2117–2122. [PubMed] [Google Scholar]
  24. Korsmeyer S. J., Arnold A., Bakhshi A., Ravetch J. V., Siebenlist U., Hieter P. A., Sharrow S. O., LeBien T. W., Kersey J. H., Poplack D. G. Immunoglobulin gene rearrangement and cell surface antigen expression in acute lymphocytic leukemias of T cell and B cell precursor origins. J Clin Invest. 1983 Feb;71(2):301–313. doi: 10.1172/JCI110770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Landay A., Gartland G. L., Clement L. T. Characterization of a phenotypically distinct subpopulation of Leu-2+ cells that suppresses T cell proliferative responses. J Immunol. 1983 Dec;131(6):2757–2761. [PubMed] [Google Scholar]
  26. Lanier L. L., Loken M. R. Human lymphocyte subpopulations identified by using three-color immunofluorescence and flow cytometry analysis: correlation of Leu-2, Leu-3, Leu-7, Leu-8, and Leu-11 cell surface antigen expression. J Immunol. 1984 Jan;132(1):151–156. [PubMed] [Google Scholar]
  27. Lanier L. L., Phillips J. H., Warner N. L., Babcock G. F. A human natural killer cell-associated antigen defined by monoclonal antibody anti-Leu (NKP-15): functional and two-color flow cytometry analysis. J Leukoc Biol. 1984 Jan;35(1):11–17. doi: 10.1002/jlb.35.1.11. [DOI] [PubMed] [Google Scholar]
  28. Ledbetter J. A., Evans R. L., Lipinski M., Cunningham-Rundles C., Good R. A., Herzenberg L. A. Evolutionary conservation of surface molecules that distinguish T lymphocyte helper/inducer and cytotoxic/suppressor subpopulations in mouse and man. J Exp Med. 1981 Feb 1;153(2):310–323. doi: 10.1084/jem.153.2.310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Linch D. C., Knott L. J., Thomas R. M., Harper P., Goldstone A. H., Davis E. G., Levinski R. J. T cell regeneration after allogeneic and autologous bone marrow transplantation. Br J Haematol. 1983 Mar;53(3):451–458. doi: 10.1111/j.1365-2141.1983.tb02046.x. [DOI] [PubMed] [Google Scholar]
  30. Mangan K. F., Hartnett M. E., Matis S. A., Winkelstein A., Abo T. Natural killer cells suppress human erythroid stem cell proliferation in vitro. Blood. 1984 Feb;63(2):260–269. [PubMed] [Google Scholar]
  31. Nadler L. M., Stashenko P., Hardy R., van Agthoven A., Terhorst C., Schlossman S. F. Characterization of a human B cell-specific antigen (B2) distinct from B1. J Immunol. 1981 May;126(5):1941–1947. [PubMed] [Google Scholar]
  32. Noel D. R., Witherspoon R. P., Storb R., Atkinson K., Doney K., Mickelson E. M., Ochs H. D., Warren R. P., Weiden P. L., Thomas E. D. Does graft-versus-host disease influence the tempo of immunologic recovery after allogeneic human marrow transplantation? An observation on 56 long-term survivors. Blood. 1978 Jun;51(6):1087–1105. [PubMed] [Google Scholar]
  33. Oi V. T., Glazer A. N., Stryer L. Fluorescent phycobiliprotein conjugates for analyses of cells and molecules. J Cell Biol. 1982 Jun;93(3):981–986. doi: 10.1083/jcb.93.3.981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rappeport J. M., Dunn M. J., Parkman R. Immature T lymphocytes in the peripheral blood of bone marrow transplant recipients. Transplantation. 1983 Dec;36(6):674–680. doi: 10.1097/00007890-198336060-00018. [DOI] [PubMed] [Google Scholar]
  35. Reinherz E. L., Parkman R., Rappeport J., Rosen F. S., Schlossman S. F. Aberrations of suppressor T cells in human graft-versus-host disease. N Engl J Med. 1979 May 10;300(19):1061–1068. doi: 10.1056/NEJM197905103001901. [DOI] [PubMed] [Google Scholar]
  36. Schroff R. W., Gale R. P., Fahey J. L. Regeneration of T cell subpopulations after bone marrow transplantation: cytomegalovirus infection and lymphoid subset imbalance. J Immunol. 1982 Nov;129(5):1926–1930. [PubMed] [Google Scholar]
  37. Stashenko P., Nadler L. M., Hardy R., Schlossman S. F. Characterization of a human B lymphocyte-specific antigen. J Immunol. 1980 Oct;125(4):1678–1685. [PubMed] [Google Scholar]
  38. Storb R., Ochs H. D., Weiden P. L., Thomas E. D. Immunologic reactivity in marrow graft recipients. Transplant Proc. 1976 Dec;8(4):637–639. [PubMed] [Google Scholar]
  39. Witherspoon R. P., Lum L. G., Storb R., Thomas E. D. In vitro regulation of immunoglobulin synthesis after human marrow transplantation. II. Deficient T and non-T lymphocyte function within 3-4 months of allogeneic, syngeneic, or autologous marrow grafting for hematologic malignancy. Blood. 1982 Apr;59(4):844–850. [PubMed] [Google Scholar]
  40. de Bruin H. G., Astaldi A., Leupers T., van de Griend R. J., Dooren L. J., Schellekens P. T., Tanke H. J., Roos M., Vossen J. M. T lymphocyte characteristics in bone marrow-transplanted patients. II. Analysis with monoclonal antibodies. J Immunol. 1981 Jul;127(1):244–251. [PubMed] [Google Scholar]

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