Summary
In patients with severe aplastic anemia (SAA), lymphocyte subpopulations were examined for the presence of HLA-DR and 2H4 (suppressor/inducer subset) antigen-expressing cells by flow cytometric analysis. Investigations were performed on peripheral blood lymphocytes before and after therapy with antithymocyte globulin (ATG) and methylprednisolone (MP), as well as on bonemarrow lymphocytes before therapy. Before treatment, only the absolute numbers of CD4+ T cells and the CD4+HLA−DR+/CD8+HLA-DR+ activated T cell ratio were significantly decreased (p<0.01 and p<0.001, respectively). Following successful ATG/MP treatment, a decrease in the CD4+/CD8+T cell ratio was found. Regarding the suppressor/inducer subset, only absolute numbers of CD4+/2H4+ cells were somewhat higher in treated patients; the percentages were the same in all groups of patients. Studies performed on bonemarrow lymphocytes showed significantly decreased percentages of CD4+ and CD8+ T lymphocytes, which also express HLA-DR antigen. No significant changes in the distribution of activated T cells following ATG/MP therapy were found, suggesting that these cells play no major role in the pathogenesis of the disease.
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Bacigalupo A, Giordano D, Van Lint MT, Vimercati R and Marmont AM (1979) Bolus methylprednisolone in severe aplastic anemia. N Engl J Med 300: 501–502
Bacigalupo A, Podesta M, Frassini T, Piaggio G, Van Lint M, Raffe M, Repetto M, Marmont A (1982) Generation of CFU-C suppressor T cells in vitro. A multistep process. Br J Haematol 52: 421–427
Camitta B, O'Reilly RJ, Sensebrenner L, Rappeport J, Champlin R, Doney K, August C, Hoffmann RG, Kirkpatrick D, Stuart R, Santos G, Parkman R, Gale RP, Storb R, Nathan D (1983) Antithoracic duct lymphocyte globulin therapy of severe aplastic anemia. Blood 62: 883–888
Carney WP, Iaciviello V, Hirsch MS (1983) Functional properties of T lymphocytes and their subsets in cytomegalovirus mononucleosis. J Immunol 130: 390–393
Champlin R, Ho W, Gale RP (1983) Antithymocyte globulin treatment in patients with aplastic anemia: a prospective randomized trial. N Engl J Med 308: 113–118
De Waele M, Thilemans C, Van Camp BK (1983) Immunoregulatory T cells in mononucleosis and toxoplasmosis. N Engl J Med 305: 228–232
De Waele M, Naessens A, Foulon W, Van Camp BK (1985) Activated T cells with suppressor/cytotoxic phenotype in acute toxoplasma gondii infection. Clin Exp Immunol 62: 256–261
Falcao RP, Voltarelli JC, Bottura CT (1985) T lymphocyte subpopulations in the peripheral blood and bone marrow of patients with aplastic anemia. Blut 50: 103–107
Fischer M, Lechner K, Hinterberger W, Niessner H, Pabinger I, Duczak R, Neumann E, Korninger C, Deutsch E (1985) Deficiency of fibrinogen and factor VIII following treatment of severe aplastic anemia with antithymocyte globulin and high-dose methylprednisolone. Scand J Haematol 34: 312–316
Freundlich B, Jimenez SA (1987) Phenotype of peripheral blood lymphocytes in patients with progressive systemic sclerosis: activated T lymphocytes and the effect of D-penicillamin therapy. Clin Exp Immunol 69: 375–384
Gascon P, Zoumbus NC, Scala G, Djeu JY, Moore JG, Young NS (1985) Lymphokine abnormalities in aplastic anemia: implications for the mechanism of action of anti thymocyte globulin. Blood 65: 407–413
Gluckman E, Marmont A, Speck B, Gordon Smith (1984) Immunosuppressive treatment of aplastic anemia as an alternative treatment for bone marrow transplantation. Semin Hematol 21: 11–19
Hafler D, Fox DA, Manning ME, Schlossmann SF, Reinherz EL, Weiner H (1985) In vivo activated T lymphocytes in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. N Engl J Med 312: 1405–1411
Hinterberger W, Geissler K, Fischer M, Kabrna E, and Hoecker P (1985) Failure of identical twin bone marrow to restore haemopoiesis in two patients with severe aplastic anemia (SAA) without immunosuppression. Exp Haematol 13: [Suppl 17] 66
Hinterberger-Fischer M, Hinterberger W, Hoecker P, Schmidmeier W, Gadner H, Geissler K, Kos M, Schwarzinger I, Neumann E, Niessner W, Schindler J, Lechner K (1986) Treatment of severe aplastic anemia with combined immunosuppression (anti thymocyte globulin and high dose methyl-prednisolone). Acta Haematol 76: 196–201
Hinterberger W, Adolf G, Aichinger G, Dudczak R, Geibler K, Höcker P, Huber C, Kahls P, Knapp W, Köller U, Lechner K, Volc-Platzer B (1988) Further evidence for lymphokine overproduction in severe aplastic anemia. Blood 72: 266–272
Hokland P, Kernstrup G, Griffin JD, Ellegard J (1986) Analysis of leukocyte differentiation antigens in blood and bone marrow from preleukemia (refractory anemia) patients using monoclonal antibodies. Blood 67: 898–902
Holter W, Majdic O, Liszka K, Stockinger H, Knapp W (1985) Kinetics of activation antigen expression by in vitro stimulated human T lymphocyts. Cell Immunol 90: 322–329
Huang AT, Mold NG, Zhang SF (1987) Antithymocyte globulin stimulates human haemopoietic progenitor cell. Proc Natl Acad Sci USA 84: 5942–5946
Hunter RF, Mold NG, Mitchell RB, Huang A (1985) Differentiation of normal bone marrow and HL 60 cells induced by antithymocyte globulin. Proc Natl Acad Sci USA 84: 4823–4827
Janossy G, Tidman N, Papageorgeou ES, Kung PC, Goldstein G (1981) Distribution of T lmyphocyte subsets in the human bone marrow and thymus. An analysis with monoclonal antibodies. J Immunol 126: 1608–1613
Kagan W, Ascenaso J, Pahwa R, Hansen R, Goldstein G, Valera G, Moore M, Good R (1976) Aplastic anemia: presence in human bone marrow of cells that suppress myelopoiesis. Proc Natl Acad Sci 3: 2890–2895
Koeller U, Majdic O, Liszka K, Stockinger H, Pabinger-Fasching I, Lechner K, Knapp W (1986) Lymphocytes of haemophilia patients treated with clotting factor concentrates display activation linked cell surface antigens. Clin Exp Immunol 59: 613–622
Kuriyama K, Tomonaga M, Jinnati I, Matsuo T, Yoshida Y, Ichimaru M (1984) Reduced helper (OKT4+): suppressor (OKT8+) T ratios in aplastic anemia: relation to immunosuppressive therapy. Br J Haematol 57: 329–336
Letvin NL, Morimoto G, Aldrich WR, Schlossman SF (1986) Definition of the T lymphocyte inducer of suppression in primates using a monoclonal antibody. Cell Immunol 94: 360–368
Morimoto C, Letvin NL, Distaso JA, Brown HM, Schlossman SF (1986) The cellular basis for the induction of antigen specific T8 suppressor cells. Eur J Immunol 16: 198–204
Morimoto C, Letvin NL, Distaso JA, Brown HM, Schlossman SF (1986) The isolation and characterization of the human suppressor inducer T cell subset. Eur J Immunol 16: 1508–1515
Morimoto C, Steinberg AD, Letvin NL, Hagan M, Takeuchi T, Dalez T, Levine H, Schlossman SF (1987) A defect of immunoregulatory T cell subsets in systemic lupus erythematosus patients demonstrated with anti-2H4 antibody. J Clin Invest 79: 762–768
Morimoto C, Hafler DA, Weiner HL, Letvin NL, Hagan M, Daley J, Schlossman SF (1987) Selective loss of the suppressor/inducer T cell subset in progressive multiple sclerosis. N Engl J Med 316: 67–72
Pitzalis K, Kingsley G, Murphy J, Panayi G (1987) abnormal distribution of the helper- inducer and suppressorinducer T lymphocyte subsets in the rheumatoid joint. Clin Immunol Immunopathol 45: 252–258
Platanias L, Gascon P, Bielory L, Zoumbos N, Djeu J, Siegel J, Nienhuis L and Young N (1985) Alternations in lymphocyte phenotype and lymphokines in patients with aplastic anemia following anti/ thymocyte glublin (ATG) therapy (abstract). Blood [Suppl] 66: 374
Platanias K, Gascon P, Bielory L, Griffith P, Nienhuis A, Young N (1987) Lymphocyte phenotype and lymphokines following anti-thymocyte globulin therapy in patients with aplastic anemia. Br J Haematol 66: 437–443
Reinherz EL, Kung PC, Pesandro JM, Ritz G, Goldstein G, Schlossman SF (1979). Ia determinants on human T cells defined by monoclonal antibody: activation stimuli required for expression. J Exp Med 150: 1472–1477
Schober I, Braun R, Reiser H, Munk K, Leroux M, Kirchner H (1984) Ia- positive T lymphocytes are the producer cells of interferon gamma. Exp cell Res 152: 348–355
Speck B, Gratwohl A, Nissen C, Leibundgut U, Ruggero D, Osterwalder B, Burri HP, Cornn P, Jeannet M (1981) Treatment of severe aplastic anemia with anti lymphocyte globuline or bone marrow transplantation. Br Med J 281: 860–863
Speck B, Gratwohl A, Nissen C, Osterwalder B, Wursch A, Tichelli A, Lori A, Reusser P, Jeannet M, Signer E (1986) Treatment of severe aplastic anemia. Exp Hematol 14: 126–132
Stockinger H, Majdic O, Liszka Ch, Koeller U, Holter W, Peschel C, Bettelheim P, Gisslinger H, Knapp W (1986) T 14, a non modulating 150 KD T cell antigen. In: Reinherz E, Haynes BF, Nadler LM, Bernstein ID (eds) Leukocyte typing II, vol 1. Springer, Berlin Heidelberg New York, pp 513–524
Sullivan R, Quesenberry P, Parkman R, Zuckermann KS, Levey RH, Rappaport J, Ryan M (1980) Aplastic anemia: lack of bone marrow lymphocytes on in vitro granulopoiesis. Blood 56: 625–630
Torok-Storb BJ, Sieff C, Storb R, Admason J, Thomas ED (1980) In vitro tests for distinguishing possible immune mediated aplastic anemia identified by microfluorometry. Blood 55: 211–215
Torok Storb BJ, Donez K, Sale G, Thomas Ed, Storb R (1985) Subsets of patients with aplastic anemia identified by microfluorometry. N Engl J Med 312: 1015–1022
Zu DTY, Winchester RJ, Fu SM, Gibovsky A, Ko HS, Kunkel HG (1980) Peripheral blood Ia positive T cells: increases in certain diseases and after immunization. J Exp Med 151: 91–99 Semin Hematol 21: 11–19
Zoumbos NC, Ferris WO, Hsu SM, Goodmans S, Griffith P, Sharrow SO, Humphries KR, Nienhuis AW, Young N (1984) Analysis of lymphocyte subsets in patients with aplastic anemia. Br J Haematol 58: 95–105
Zoumbos NC, Gascon P, Djeu JY, Trost SR, Young N (1985) circulating activated suppressor lymphocytes in aplastic anemia. N Engl J Med 312: 257–264
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Köller, U., Hinterberger, W., Gschwandtler, L. et al. Identification of activated T cells and the suppressor/inducer subset in patients suffering from severe aplastic anemia. Blut 58, 21–26 (1989). https://doi.org/10.1007/BF00320231
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DOI: https://doi.org/10.1007/BF00320231