The authors briefly review recent experimental advances in elucidating the role of dual T cell receptor (TCR)-expressing lymphocytes in the developement of diseases with special emphasis on autoimmunity. Moreover, they summarize present knowledge about these cells concerning their proportion among peripheral blood mononuclear cells, their functionality, and their impact on allorecognition and memory both in humans and in mice. Finally, they describe disease-associated clonal expansions of dual TCR-expressing cells in humans, most of which have been observed in peripheral T cell malignancies. Other cases occurred in inflammatory bowel disease and in HIV infection. They propose that expression of two distinct TCR on malignant T lymphocytes might be much higher than is suggested by the few cases described so far, and that their presence might impinge on therapeutic immunization strategies which make use of the TCR itself as a target.

1.
Padovan E, Casorati G, Dellabona P, Meyer S, Brockhaus M, Lanzavecchia A: Expression of two T cell receptor α chains: Dual T cells. Science 1993;262:422–424.
2.
Heath WR, Carbone FR, Bertolino P, Kelly J, Cose S, Miller JFAP: Expression of two T cell receptor α chains on the surface of normal murine T cells. Eur J Immunol 1995;25:1617–1623.
3.
Padovan E, Casorati G, Dellabona P, Giachino C, Lanzavecchia A: Dual receptor T-cells. Implications for alloreactivity and autoimmunity. Ann NY Acad Sci 1995;756:66–67.
4.
Elliott JI, Altmann DM: Dual T cell receptor α chain T cells in autoimmunity. J Exp Med 1995;183:953–960.
5.
Elliott JI: Selection of dual Vα T cells. Eur J Immunol 1998;28:2115–2123.
6.
Davodeau F, Peyrat M-A, Romagné F, Necker A, Hallet M-M, Vié H, Bonneville M: Dual T cell receptor β chain expression on human T lymphocytes. J Exp Med 1995;181:1391–1398.
7.
Padovan E, Giachino C, Cella M, Valitutti S, Acuto O, Lanzavecchia A: Normal T lymphocytes can express two different T cell receptor β chains: Implications for the mechanism of allelic exclusion. J Exp Med 1995;181:1587–1591.
8.
Munthe LA, Blichfeldt E, Sollien A, Dembic Z, Bogen B: T cells with two Tcr β chains and reactivity to both MHC/idiotypic peptide and superantigen. Cell Immunol 1996;170:283–290.
9.
von Boehmer H: Positive selection of lymphocytes. Cell 1994;76:219–228.
10.
Balomenos D, Balderas RS, Mulvany KP, Kaye J, Kono DH, Theofilopoulos AN: Incomplete T cell receptor Vβ allelic exclusion and dual Vβ-expressing cells. J Immunol 1995;155:3308–3312.
11.
Davodeau F, Peyrat M-A, Houde I, Hallet M-M, De Libero G, Vié H, Bonneville M: Surface expression of two distinct functional antigen receptors on human γδ T cells. Science 1993;260:1800–1803.
12.
Peyrat MA, Davodeau F, Houde I, Romagne F, Necker A, Leget C, Cervoni JP, Cerf-Bensussan N, Vie H, Bonneville M, Hallet MM: Repertoire analysis of human peripheral blood lymphocytes using a human Vδ3 region-specific monoclonal antibody. J Immunol 1995;155:3060–3067.
13.
Simpson E, Chandler P, Sponaas A, Millrain M, Dyson PJ: T cells with dual antigen specificity in T cell receptor transgenic mice rejecting allografts. Eur J Immunol 1995;25:2813–2817.
14.
Zavazava N, Kabelitz D: Alloreactivity and apoptosis in graft rejection and transplantation tolerance. J Leukoc Biol 2000;68:167–174.
15.
Malissen M, Trucy J, Letourneur F, Rebaï N, Dunn DE, Fitch FW, Hood L, Malissen B: A T cell clone expresses two cell receptor α genes but uses one αβ heterodimer for allorecognition and self MHC-restricted antigen recognition. Cell 1988;55:49–59.
16.
Lee WT, Shiledar-Baxi V, Winslow GM, Mix D, Murphy DB: Self-restricted dual receptor memory T cells. J Immunol 1998;161:4513–4519.
17.
Lee WT, Cole-Calkins J, Street NE: Memory T cell development in the absence of specific antigen priming. J Immunol 1996;157:5300–5307.
18.
Hardardottier F, Baron JL, Janeway A Jr: T cells with two functional antigen-specific receptors. Proc Natl Acad Sci USA 1995;92:354–358.
19.
Mackay CR, Marston WL, Dudler L: Naive and memory T cells show distinct pathways of lymphocyte recirculation. J Exp Med 1990;171:801–817.
20.
Nossal GJV: Negative selection of lymphocytes. Cell 1994;76:229–239.
21.
Zal T, Weiss S, Mellor A, Stockinger B: Expression of a second receptor rescues self-specific T cells from thymic deletion and allows activation of autoreactive effector function. Proc Natl Acad Sci USA 1996;93:9102–9107.
22.
Blichfeldt E, Munthe LA, Røtnes J, Bogen B: Dual T cell receptor T cells have a decreased sensitivity to physiological ligands due to reduced density of each T cell receptor. Eur J Immunol 1996;26:2876–2884.
23.
Fossati G, Cooke A, Papafio RQ, Haskins K, Stockinger B: Triggering a seond T cell receptor on diabetogenic T cells can prevent induction of diabetes. J Exp Med 1999;190:577–583.
24.
Sarukhan A, Garcia C, Lanoue A, von Boehmer H: Allelic inclusion of T cell receptor α genes poses an autoimmune hazard due to low-level expression of autospecific receptors. Immunity 1998;8:563–570.
25.
Hinz T, Marx S, Nerl C, Kabelitz D: Clonal expansion of γδ T cells expressing two distinct T-cell receptors. Br J Haematol 1996;94:62–64.
26.
Metzger R, Heckl-Östreicher B, Nerl C, Schondelmaier S, Kabelitz D: Immunological studies of γδ T cells in a case of large granular lymphocyte (LGL) leukemia: Leukemic γδ+ T cells are resistant to growth stimulation in vitro but respond to interferon-α treatment in vivo. Leuk Res 1992;16:1087–1095.
27.
Boehrer S, Hinz T, Schui DK, Harder S, Chow KU, Schneider B, Hoelzer D, Mitrou PS, Weidmann E: T-large granular lymphocyte leukaemia with natural killer cell-like cytotoxicity and expression of two different α- and β-cell receptor chains. Br J Haematol 2001;112:201–203.
28.
Hinz T, Kabelitz D: Identification of the T-cell receptor alpha variable (TRAV) gene(s) in T-cell malignancies. J Immunol Methods 2000;246:145–148.
29.
Weidmann E, Hinz T, Klein S, Schui DK, Harder S, Kriener S, Kabelitz D, Hoelzer D, Mitrou PS: Cytotoxic hepatosplenic γδ T-cell lymphoma following acute myeloid leukemia bearing two distinct γ chains of the T-cell receptor. Biologic and clinical features. Haematologica 2000;85:1024–1031.
30.
Weidmann E: Hepatosplenic T cell lymphoma. A review on 45 cases since the first report describing the disease as a distinct lymphoma entity in 1990. Leukemia 2000;14:991–997.
31.
Söderström K, Bucht A, Halapi E, Grönberg A, Magnusson I, Kiessling R: Increased frequency of abnormal γδ T cells in blood of patients with inflammatory bowel diseases. J Immunol 1996;156:2331–2339.
32.
Giacomelli R, Parzanese I, Frieri G, Passacantando A, Pizutto F, Pimpo T, Cipriani P, Viscido A, Caprilli R, Tonietti G: Increase of circulating γδ T lymphocytes in the peripheral blood of patients affected by active inflammatory bowel disease. Clin Exp Immunol 1994;98:83–88.
33.
Autran B, Triebel F, Katlama C, Rozenbaum W, Hercend T, Debré P: T cell receptor gamma/delta+ lymphocyte subsets during HIV infection. Clin Exp Immunol 1989;75:206–210.
34.
Hinz T, Wesch D, Friese K, Reckziegel A, Arden B, Kabelitz D: T cell receptor γδ repertoire in HIV-infected individuals. Eur J Immunol 1994;24:3044–3049.
35.
Kabelitz D, Wesch D, Hinz T: γδ T cells, their T cell receptor usage and role in human diseases. Springer Semin Immunopathol 1999;21:55–75.
36.
Wesch D, Hinz T, Kabelitz D: Analysis of the TCR Vγ repertoire in healthy donors and HIV-1-infected individuals. Int Immunol 1998;10:1067–1075.
37.
Taupin J-L, Halary F, Déchanet J, Peyrat M-A, Ragnaud J-M, Bonneville M, Moreau J-F: An enlarged subpopulation of T lymphocytes bearing two distinct γδ TCR in an HIV-positive patient. Int Immunol 1998;11:545–552.
38.
Semenzato G, Zambello R, Starkebaum G, Oshimi K, Loughran TP Jr: The lymphoproliferative dissease of granular lymphocytes: Updated criteria for diagnosis. Blood 1997;89:256–260.
39.
Wong CP, Levy R: Recombinant adenovirus vaccine encoding a chimeric T-cell antigen receptor induces protective immunity against a T-cell lymphoma. Cancer Res 2000;60:2689–2695.
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