[en] In the context of allogeneic bone marrow transplantation, an accurate estimate of the risk of developing graft-versus-host
disease GVHD. is of major interest. The pre-transplant frequency of donor’s helper T-lymphocyte precursors HTLp.
directed against host’s antigens may be helpful in predicting this risk. This technique relies on an indirect measurement of
interleukin-2 IL-2. secreted by the HTLp, as assessed by the proliferation of an IL-2 dependent cell line. Many authors use
the murine CTLL-2 cell line in this assay, but these cells do not respond to the presence of minute amounts of IL-2 in the
culture medium, and thus do not discriminate between the absence or the presence of very low levels of IL-2. We therefore
decided to compare CTLL-2 with another IL-2 dependent cell line, the murine A9.12 cell line. A comparison was made
using serial dilutions of recombinant human IL-2, limiting dilutions of baby hamster kidney BHK. cells transfected with
human IL-2 gene and in the context of clinical tests performed for the detection of pre-transplant HTLp. Both the sensitivity
and reliability of the tests were better using A9.12. We conclude that the A9.12 cell line might be a more suitable tool for
pre-transplant HTLp determinations before allogeneic bone marrow transplantation or whenever low IL-2 levels are to be
measured.
Research center :
UCL, Immunohématologie
Disciplines :
Biotechnology
Author, co-author :
Winandy, Marie ; Université Catholique de Louvain - UCL > Immunohématologie
Lewalle, Philippe
Deneys, Véronique
Ferant, Augustin
De Bruyère, Marc
Language :
English
Title :
Improved IL-2 detection for determination of helper T lymphocyte precursor frequency in limiting dilution assay
Publication date :
1998
Journal title :
Journal of Immunological Methods
ISSN :
0022-1759
eISSN :
1872-7905
Publisher :
Elsevier Science
Volume :
215
Pages :
81-94
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Appleton, A.L., Sviland, S., 1993. Pathogenesis of GVHD: role of herpes viruses. Bone Marrow Transplant. 11, 349.
Appleton, A.L., Sviland, S., Peiris, J.S.M., Taylor, C.E., Wilkes, J., Green, M.A., Pearson, A.D.J., Procotor, S.J., Hamilton, P.J., Cant, A.J., Malcolm, A.J., 1995. Role of target organ infection with cytomegalovirus in the pathogenesis of GVHD. Bone Marrow Transplant. 15, 557.
Batchelor, J.R., Schwarer, A.P., Yin, Z.J., Barrett, A.J., Goldman, J.M., Lechler, R.I., 1993. Helper T-lymphocyte precursor frequencies predict risks of GVHD in bone marrow transplantation. Transplant. Proc. 25, 1237.
Bearman, S., Mori, M., Beatty, P.G., Meyer, W.G., Buckner, C.D., Petersen, F.B., Sanders, J.E., Anasetti, C., Martin, P., Appelbaum, F.R., Hansen, J.A., 1994. Comparison of morbidity and mortality after marrow transplantation from HLA-genotypically identical unrelated donors. Bone Marrow Transplant. 13, 31.
Boström, L., Ringdén, O., Forsgren, M., 1992. Strong donor mononuclear cell reactivity for herpes simplex virus antigen in immune donor/recipient pair is associated with GVHD. Transplant. Proc. 24, 376.
Bouma, G.J., Shanz, U., Oudshoorn, M., van der Meer-Prins, P.M.W., Roelen, D.L., van Rood, J.J., Claas, F.H.J., 1996. A cell-saving non-radioactive limiting dilution analysis-assay for the combined determination of helper and cytotoxic T lymphocyte precursor frequencies. Bone Marrow Transplant. 17, 19.
Bradley, B.A., Jeannet, M., 1993. Unrelated donor bone marrow transplantation - the role of histocompatibility. Bone Marrow Transplant. 12, 29, suppl. 4.
Brinchmann, J.E., Doblourg, J.H., Heger, B.H., Haaiheim, L.L., Sannes, M., Egeland, T., 1994. Expression of costimulatory molecule CD28 on T cells in human immunodeficiency virus type 1 infection: functional and clinical correlations. J. Infect. Dis. 169, 730.
Bunjes, D., Theobald, M., Nierle, T., Arnold, R., Heimpel, H., 1995. Presence of host-specific IL-2-secreting T helper cell precursors correlates closely with active primary and secondary chronic GVHD. Bone Marrow Transplant. 15, 727.
Burns, J., Littlefield, K., 1993. A role for antigen presenting cells and bacterial superantigens in reversal of human T lymphocyte anergy. Eur. J. Immunol. 23, 3300.
Collette, Y., Chang, H.L., Cerdan, C., Chambost, H., Algarte, M., Mawas, C., Imbert, J., Burny, A., Olive, D., 1996. Specific Th1 cytokine down-regulation associated with primary clinically derived human immunodeficiency virus type 1 Nef gene-induced expression. J. Immunol. 156, 360.
Conradt, H.S., Nimtz, M., Dittmar, K.E., Lindemaier, W., Hoppe, J., Hauser, H., 1989. Expression of human IL-2 in recombinant baby hamster kidney, Ltk- and Chinese hamster ovary cells. Structure of O-linked carbohydrate chains and their location within the polypeptide. J. Biol. Chem. 29, 17368.
DeBruyne, L.A., Renlund, D.G., Bishop, D.K., 1995. Evidence that human cardiac allograft acceptance is associated with a decrease in donor-reactive T-lymphocytes. Transplantation 59, 778.
de Gast, G.C., Mickelson, E.M., Beatty, P.G., Amos, D., Sullivan, K.M., Schoch, H.G., Thomas, E.D., Hansen, J.A., 1992. Mixed leukocyte culture reactivity and GVHD in HLA-identical marrow transplantation for leukemia. Bone Marrow Transplant. 9, 87.
De Maria, R., Todaro, M., Stassi, G., Di Blasi, F., Giordano, M., Galluzzo, A., Giordano, C., 1994. Defective T cell receptor/CD3 complex signalling in human type I diabetes. Eur. J. Immunol. 24, 999.
den Haan, J.M.M., Sherman, N.E., Blokland, E., Huczko, E., Koning, F., Drijfhout, J.W., Skipper, J., Shabanowitz, J., Hunt, D.F., Engelhard, V.H., Goulmy, E., 1995. Identification of GVHD-associated human minor histocompatibility antigens. Lancet 268, 1476.
Ferrara, J.L.M., 1994. Paradigm shift for graft-versus-host disease. Bone Marrow Transplant. 14, 183.
Galdiero, M., Cipollaro de l'Ero, G., Folgore, A., Cappello, M., Giobbe, A., Sasso, F.S., 1994. Effect of irradiation doses on alterations in cytokine release by monocytes and lymphocytes. J. Med. 25, 23.
Gillis, S., Perm, M.M., Ou, W., Smith, K.A., 1978. T cell growth factor: parameters of production and a quantitative microassay for activity. J. Immunol. 120, 2027.
Goulmy, E., Bockland, E., Gratama, J.W., Zwaan, F.E., van Rood, J.J., 1985. Host-directed cytotoxic activity in bone marrow-grafted patients. Transplant. Proc. 17, 725.
Gribben, J.G., Guinan, E.C., Boussiotis, V.A., Ke, X.Y., Linsley, L., Sieff, C., Gray, G.S., Freeman, G.J., Nadler, L.M., 1996. Complete blockade of B7 family mediated costimulation is necessary to induce human alloantigen-specific anergy: a method to ameliorate graft-versus-host disease and extend the donor pool. Blood 87, 4887.
Hansen, J.A., Petersdorf, E.W., Choo, S.Y., Marin, P.J., Anasetti, C., 1995. Marrow transplantation from HLA partially matched relatives and unrelated donors. Bone Marrow Transplant. 15, s128, suppl 2.
Hornick, P.I., Brookes, P.A., Mason, P.D., Taylor, K.M., Yacoub, M.H., Rose, M.L., Batchelor, R., Lechler, R.I., 1997. Optimizing a limiting dilution culture system for quantifying the frequency of interleukin-2-producing alloreactive helper T lymphocytes. Transplantation 64, 472.
Iglewicz, B., Hoaglin, D.C., 1993. How to detect and handle outliers. The ASQC Basis References in Quality Control: Statistical Techniques, Vol. 16.
Kaminski, E., Hows, J., Man, S., Brookes, P., Hughes, T., Avakian, O., Goldman, J.M., Batchelor, J.R., 1989. Prediction of GVHD by frequency analysis of cytotoxic T cells after unrelated donor bone marrow transplantation. Transplantation 48, 608.
Keever-Taylor, C.A., Passweg, J., Kawanishi, Y., Casper, J., Flomenberg, N., Baxter-Lowe, L.A., 1997. Association of donor-derived host-reactive cytolytic and helper T cells with outcome following alternative donor T cell-depleted bone marrow transplantation. Bone Marrow Transplant. 19, 1001.
Lewalle, P., Hensel, N., Guimares, A., Couriel, D., Jiang, Y.Z., Mavroudis, D., Barrett, A.J., 1996. Helper and cytotoxic lymphocyte responses to chronic myeloid leukaemia: implications for adoptive immunotherapy with T cells. Br. J. Haematol. 92, 587.
Lohr, H.F., Schlaak, J.F., Gerken, G., Fleischer, B., Dienes, H.P., 1994. Phenotypical analysis and cytokine release of liver-infiltrating and peripheral blood T-lymphocytes from patients with chronic hepatitis of different etiology. Liver 14, 161.
Menu, E., Jankovic, D.L., Theze, J., David, V., Chaouat, G., 1990. Immunoactive products of human placenta (III): characterization of an inhibitor affecting lymphocyte proliferation. Reg. Immunol. 3, 254.
Muluk, S.C., Clerici, M., Via, C.S., Weir, M.R., Kimmel, P.L., Shearer, G.M., 1991. Correlation of in vitro CD4+ T helper cell function with clinical graft status in immunosuppressed kidney transplant recipients. Transplantation 52, 284.
Nierle, T., Bunjes, D., Arnold, R., Heimpel, H., Theobald, M., 1993. Quantitative assessment of posttransplant host-specific IL-2-secreting T helper cells precursors in patients with and without acute GVHD after allogeneic HLA-identical sibling bone marrow transplantation. Blood 81, 841.
Potolicchio, I., Brookes, P.A., Madrigal, A., Lechler, R.I., Sorrentino, R., 1996. HLA-DPB1 mismatch at position 69 is associated with high helper T lymphocyte precursor frequencies in unrelated bone marrow transplant pairs. Transplantation 62, 1347.
Rep, M.H., Hintzen, R.Q., Polman, C.H., van Lier, R.A., 1996. Recombinant interferon beta blocks proliferation but enhances interleukin-10 secretion by activated human T cells. J. Neuroimmunol. 67, 111.
Roosnek, E., Hogendijk, S., Zawadynski, S., Speiser, D., Tiercy, J.M., Helg, C., Chapuis, B., Gratwhol, A., Gmür, J., Seger, R., Jeannet, M., 1993. The frequency of pretransplant donor cytotoxic T cell precursors with anti-host specificity predicts survival of patients transplanted with bone marrow from donors other than HLA-identical siblings. Transplantation 56, 691.
Schanz, U., Roelen, D.L., Kardol, M.J., van Rood, J.J., Claas, F.H.J., 1994. The relative radioresistance of interleukin-2 production by human peripheral blood lymphocytes: consequences for the development of a new limiting dilution assay for the enumeration of T lymphocyte precursor frequencies. J. Immunol. Meth. 169, 221.
Schulick, R.D., Weir, M.B., Miller, M.W., Cohen, D.J., Bermas, B.L., Shearer, G.M., 1993. Longitudinal study of in vitro CD4+ T helper cell function in recently transplanted renal allograft patients undergoing tapering of their immunosuppressive drugs. Transplantation 56, 590.
Schwarer, A.P., Jiang, Y.Z., Brookes, P.A., Barrett, A.J., Batchelor, J.R., Goldman, J.M., Lechler, 1993. Frequency of anti-recipient alloreactive helper T-cell precursor in donor blood and GVHD after identical-sibling bone marrow transplantation. Lancet 341, 203.
Semple, J.W., Milev, Y., Cosgrave, D., Mody, M., Hornstein, A., Blanchette, V., Freedman, J., 1996. Differences in serum cytokine levels in acute and chronic autoimmune thrombocytopenic purpura: relationship to platelet phenotype and antiplatelet T cell reactivity. Blood 87, 4245.
Shih, C.C.Y., Truitt, R.L., Abramoff, P., Bortin, M.M., 1983. Relationship between IL-2 receptors and cyclosporine-induced suppression of T leukemia and T helper cells. Transplant. Proc. 15, 2394, suppl 1.
Taswell, C., 1981. Limiting dilution assays for the determination of immunocompetent cell frequencies. I. Data analysis. J. Immunol. 12, 1614.
Taswell, C., 1984. Limiting dilution assays for the determination of immunocompetent cell frequencies: III. Validity tests for single-hit Poisson model. J. Immunol. Meth. 72, 29.
Theobald, M., 1995. Allorecognition and GVHD. Bone Marrow Transplant. 15, 489.
Theobald, M., Bunjes, D., 1993. Pretransplant detection of human minor histocompatibility antigen-specific naive and memory interleukin-2 secreting T cells within class I major histocompatibility complex (MHC)-restricted CD8+ and class II MHC-restricted CD4+ T cells subsets. Blood 82, 298.
Theobald, M., Nierle, T., Bunjes, D., Arnold, R., Heimpel, H., 1992. Host-specific IL-2-secreting T cell precursors as predictors of acute GVHD in bone marrow transplantation between HLA-identical siblings. New Engl. J. Med. 327, 1613.
van der Meer, A., Joosten, I., Ruiter, J., Allebes, W.A., 1997. A single (3H) thymidine-based limiting dilution analysis to determine HTLp and CTLp frequencies for bone marrow donor selection. Bone Marrow Transplant. 20, 149.
Westendorp, M.O., Li Weber, M., Frank, R.W., Krammer, P.H., 1994. Human immunodeficiency virus type 1 Tat upregulates interleukin-2 secretion in activated T cells. J. Virol. 68, 4177.
Weston, L., Farrell, C., 1996. HTLp in human transplantations. Hum. Immunol. 47, 84.
Xun, C.Q., Thompson, J.S., Jennings, C.D., Brown, S.A., Widmer, D.B., 1994. Effect of total body irradiation, busulfancyclophosphamide or cyclophosphamide conditioning on inflammatory cytokine release and development of acute and chronic graft-versus-host disease in H-2-incompatible transplanted SCID mice. Blood 83, 2360.
Yi, Q., Ahlberg, R., Pirskanen, R., Lefvert, A.K., 1994. Acetylcholine receptor-reactive T cells in myasthenia gravis: evidence for the involvement of different subpopulations of T helper cells. J. Neuroimmunol. 50, 177.
Yoo, J., Chen, H., Kraus, T., Hirsch, D., Polyak, S., George, I., Sperber, K., 1996. Altered cytokine production and accessory cell function after HIV-1 infection. J. Immunol. 157, 1313.
Young, N.Y., Roelen, D.L., Dallman, M.J., Wood, K.J., Morris, P.J., Welsh, K.I., 1996. Enumeration of human alloreactive T lymphocyte precursor frequencies by limiting dilution analysis of IL-2 production. J. Immunol. Meth. 195, 33.
