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Characterization of the immunophenotype and the metastatic properties of a murine T-lymphoma cell line. Unexpected expression of cytoplasmatic CD4

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Summary

We report the first characterization of a mouse T-lymphoma cell line that surprisingly expresses cytoplasmatic (cy) cyCD4. Phenotypically, LBC cells are CD5+, CD8+, CD16+, CD24+, CD25+, CD2−/dim, CD3−/dim, TCRβ−/dim, TCRγδ, CD154, CD40, and CD45R. Coexpress cyTCRβ, cyCD3, cyCD4, and yet lack surface CD4 expression. Transplantation of LBC cells into mice resulted in an aggressive T-lymphoblastic lymphoma that infiltrated lymph nodes, thymus, spleen, liver, ovary, and uterus but not peripheral blood or bone marrow. LBC cells display a modal chromosome number of 39 and a near-diploid karyotype. Based on the characterization data, we demonstrated that the LBC cell line was derived from an early T-cell lymphocyte precursor. We propose that the malignant cell transformation of LBC cells could coincide with the transition stage from late double-negative, DN3 (CD4, CD8CD44−/low, CD25+) or DN4 (CD4−/low, CD8−/low, CD44, CD25) to double-positive (DP: CD4+CD8+) stage of T-cell development. LBC cells provide a T-lymphoblastic lymphoma model derived from a malignant early T-lymphocyte that can be potentially useful as a model to study both cellular regulation and differentiation of T-cells. In addition, LBC tumor provides a short latency neoplasm to study cellular regulation and to perform preclinical trials of lymphoma-related disorders.

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References

  • Campana, D.; van Dongen, J. J.; Mehta, A.; Coustan-Smith, E.; Wolvers-Tettero, I. L.; Ganeshaguru, K.; Janossy, G. Stages of T-cell receptor protein expression in T-cell acute lymphoblastic leukemia. Blood 77:1546–1554; 1991.

    PubMed  CAS  Google Scholar 

  • Coligan, J. E.; Kruisbeek, A. M.; Margulies, D. H.; Shevach, S. W. In vitro assays for mouse lymphocyte function. In: Current protocols in immunology, New York: Greene Publishing and Wiley Interscience; 1992a:3.17.2–3.17.3

    Google Scholar 

  • Coligan, J. E.; Kruisbeek, A. M.; Margulies, D. H.; Shevach, S. W. In vitro assays for mouse lymphocyte function. In: Current protocols in immunology. New York: Greene Publishing and Wiley Interscience; 1992b:3.17.8–3.17..

    Google Scholar 

  • Committee on standarized genetic nomenclature for mice. Standard karyotype of the mouse Mus musculus. J. Hered. 63:69–72; 1972.

    Google Scholar 

  • Crispe, I. N.; Moore, M. W.; Husmann, L. A.; Smith, L.; Bevan, M. J.; Shimonkevitz, R. P. Differentiation potential of subsets of CD4 CD8 thymocytes. Nature (Lond.) 329:336–339; 1987.

    Article  CAS  Google Scholar 

  • Duplay, P.; Lancki, D.; Allison, J. P. Distribution and ontogeny of CD2 expression by murine T cells. J. Immunol. 142:2998–3005; 1989.

    PubMed  CAS  Google Scholar 

  • Falini, B.; Flenghi, L.; Fagioli, M., et al. T-lymphoblastic lymphomas expressing the non-disulfide-linked form of the T-cell receptor gamma/delta: characterization with monoclonal antibodies and genotypic analysis. Blood 74:2501–2507; 1989.

    PubMed  CAS  Google Scholar 

  • Fehling, H. J.; von Böehmer, H. Early αβ T cell development in the thymus of normal and genetically altered mice. Curr. Opin. Immunol. 9:250–255; 1997.

    Article  Google Scholar 

  • Geleziunas, R.; Bour, S.; Boulerice, E.; Hiscott, J.; Wainberg, M. A. Diminution of CD4 surface protein but not CD4 messenger RNA levels in monocytic cells infected by HIV-1. AIDS 5:29–33; 1991.

    Article  PubMed  CAS  Google Scholar 

  • Groettrup, M.; Ungewiss, K.; Azogui, O.; Palacios, R.; Owen, M. J.; Hayday, A. C.; von Böehmer, H. A novel disulfide-linked heterodimer on pre-T cells consists of the T cell receptor β chain and a 33 kd glycoprotein. Cell 75:283–294; 1993.

    Article  PubMed  CAS  Google Scholar 

  • Harris, N. L.; Jaffe, E. S.; Stein, H., et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 84:1361–1392; 1994.

    PubMed  CAS  Google Scholar 

  • Ivanov, V. N.; Nikolic-Zugic, J. Biochemical and kinetic characterization of the glucocorticoid-induced apoptosis of immature CD4+CD8+ thymocytes. Int. Immunol. 10:1807–1817; 1998.

    Article  PubMed  CAS  Google Scholar 

  • Kisielow, P.; Bluthmann, H.; Staerz, U. D.; Steinmetz, M.; von Böehmer, H. Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes. Nature 333:742–746; 1988.

    Article  PubMed  CAS  Google Scholar 

  • Kisielow, P.; Leiserson, W.; von Böehmer, H. Differentiation of thymocytes in fetal organ culture: analysis of phenotypic changes accompanying the appearance of cytolytic and interleukin 2-producing cells. J. Immunol. 133:1117–1123; 1984.

    PubMed  CAS  Google Scholar 

  • Kisielow, P.; von Böehmmer, H. Development and selection of T cells: facts and puzzles. Adv. Immunol. 58:87–209; 1995.

    PubMed  CAS  Google Scholar 

  • Levelt, C.; Ehrfeld, A.; Eichmann, K. Regulation of thymocyte through CD3. I. Timepoint of ligation of CD3∈ determines clonal deletion or induction of developmental program. J. Exp. Med. 177:707–716; 1993.

    Article  PubMed  CAS  Google Scholar 

  • Lucey, D. R.; Dorsky, D. I.; Nicholson-Weller, A.; Weller, P. F. Human eosinophils express CD4 protein and bind human immunodeficiency virus 1 gp120. J. Exp. Med. 169:327–332; 1989.

    Article  PubMed  CAS  Google Scholar 

  • Luna, L. G. Manual of histologic staining of the armed forces institute of pathology. 3rd ed. New York: Blakinston-McGraw-Hill; 1960.

    Google Scholar 

  • Malissen, B.; Malissen, M. Functions of TCR and pre-TCR subunits: lessons from gene ablation. Curr. Opin. Immunol. 8:383–393; 1996.

    Article  PubMed  CAS  Google Scholar 

  • Marrack, P.; Kappler, J. Positive selection of thymocytes bearing αβ T cell receptors. Curr. Opin. Immunol. 8:215–224; 1997.

    Google Scholar 

  • Mongini, C.; Waldner, C. I.; Alvarez, E.; Roig, M. I.; Sánchez Lockhart, M.; Gravisaco, M. J.; Hajos, S. E. Induction of anti-tumour immunity in syngeneic mice by a leukaemic cell line. Scand. J. Immunol. 41:298–304; 1995.

    Article  PubMed  CAS  Google Scholar 

  • Mongini, C.; Waldner, C.; Caldas Lopes, E.; Cravisaco, M. J.; Escalada, A.; Sánchez Lockhart, M. S.; Alvarez, E.; Hajos, S. Induction of apoptosis in murine lymphoma cells by cyclosporin A. Int. J. Mol. Med., 7:431–437; 2001.

    PubMed  CAS  Google Scholar 

  • Mongini, C.; Waldner, C. I.; Roig, I.; Hajos, S. E. Growth characteristics of a murine T-cell leukemia in suspension culture. In Vitro Cell. Dev. Biol. 27:523–524; 1991.

    Google Scholar 

  • Nikolic-Zugic, J. Phenotypic and functional stages in the intrathymic development of alpha beta T cells. Immunol Today 12:65–70; 1991.

    Article  PubMed  CAS  Google Scholar 

  • O'Connor, G. T. Definition of Burkitts tumor. Int. J. Cancer 15:411–412; 1968.

    Google Scholar 

  • Plum, J.; De Smedt, M.; Verhasselt, B.; Offner, F.; Kerre, T.; Vanhecke, D.; Leclercq, C.; Vandekerckhove, B. In vitro intrathymic differentiation kinetics of human fetal liver CD34+CD38-progenitors reyeals a phenotypically defined dendritic/T-NK precursor split. J. Immunol. 162:60–68; 1999.

    PubMed  CAS  Google Scholar 

  • Rodewald, H. R.; Awad, K.; Moingeon, P.; D'Adamio, L.; Rabinowitz, D.; Shinkai, Y.; Alt, F. W.; Reinherz, E. L. FcR II/III and CD2 expression mark distinct subpopulations of immature CD4 CD8 murine thymocytes: in vivo developmental kinetics and T-cell receptor rearrangement. J. Exp. Med. 177:1079–1092; 1993.

    Article  PubMed  CAS  Google Scholar 

  • Ruggiero, R. A.; Bustuoabad, O. D.; Bonfil, R. D.; Meiss, R. P.; Pasqualini, C. D. Concomitant immunity in murine tumours of non-detectable immunogenicity. Br. J. Cancer 51:1–10; 1984.

    Google Scholar 

  • Saint-Ruf, C.; Ungewiss, K.; Groettrup, M.; Bruno, L.; Fehling, H. J.; von Böehmer, H. Analysis and expression of a cloned pre-T cell receptor gene. Science 266:1208–1212; 1994.

    Article  PubMed  CAS  Google Scholar 

  • Sánchez, M. J.; Spits, H.; Lanier, L. L.; Phillips, J. H. Human NK committed thymocytes and their relation to the T-cell lineage. J. Exp. Med. 178:1857–1866; 1993.

    Article  PubMed  Google Scholar 

  • Sattentau, Q. J.; Weiss, R. A. The CD4 antigen: physiological ligand and HIV receptor. Cell 52:631–633; 1988.

    Article  PubMed  CAS  Google Scholar 

  • Seabright, M. A rapid banding technique for human chromosomes. Lancet II:971–972; 1971.

    Article  Google Scholar 

  • Stewart, S. J.; Fujimoto, J.; Levy, R. Human T lymphocytes and monocytes bear the same Leu-3(T4) antigen. J. Immunol. 136:3773–3778; 1986.

    PubMed  CAS  Google Scholar 

  • Tifft, C. J.; Proia, R. L.; Camerini-Otero, R. D. The folding and cell surface expression of CD4 requires glycosylation. J. Biol. Chem. 267:3268–3273; 1992.

    PubMed  CAS  Google Scholar 

  • Trop, S.; Steff, A. M.; Denis, F.; Wiest, D. L.; Hugo, P. The connecting peptide domain of pT alpha dictates weak association of the pre-T cell receptor with the TCR zeta subunit. Eur. J. Immunol. 29:2187–2196; 1999.

    Article  PubMed  CAS  Google Scholar 

  • Wilson, A.; Capone, M.; MacDonald, H. R. Unexpectedly late expression of intracellular CD3epsilon and TCR gammadelta proteins during adult thymus development. Int. Immunol. 11:1641–1650; 1999.

    Article  PubMed  CAS  Google Scholar 

  • Wilson, A.; Petrie, H. T.; Scollay, R.; Shortman, K. The acquisition of CD4 and CD8 during the differentiation of early thymocytes in short-term culture. Int. Immunol. 1:605–612; 1989.

    Article  PubMed  CAS  Google Scholar 

  • Würch, A.; Biro, J.; Potocnik, A. J.; Falk, I.; Mossmann, H.; Eichmann, K. Requirement of CD3 complex-associated signaling functions for expression of rearranged T cell receptor beta VDJ genes in early thymic development. J. Exp. Med. 188:1669–1678; 1998.

    Article  PubMed  Google Scholar 

  • Yague, J.; White, J.; Coleclough, C.; Kappler, J.; Palmer, E.; Marrack, P. The T cell receptor: the alpha and beta chains define the idiotype, antigen and MHC specificity. Cell 42:81–87; 1985.

    Article  PubMed  CAS  Google Scholar 

  • Zinkernagel, R. M.; Doherty, P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major trnasplantation antigens determining T-cell restriction specificity, function and responsiveness. Adv. Immunol. 27:51–175; 1979.

    Article  PubMed  CAS  Google Scholar 

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Mongini, C., Ruybal, P., Gravisaco, M.J. et al. Characterization of the immunophenotype and the metastatic properties of a murine T-lymphoma cell line. Unexpected expression of cytoplasmatic CD4. In Vitro Cell.Dev.Biol.-Animal 37, 499–504 (2001). https://doi.org/10.1290/1071-2690(2001)037<0499:COTIAT>2.0.CO;2

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