• 1
    Chatila, T. A., Blaeser, F., Ho, N., Lederman, H. M., Voulgaropoulos, C., Helms, C. and Bowcock, A. M., JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome. J. Clin. Invest. 2000. 106: R75–R81.
  • 2
    Bennett, C. L., Christie, J., Ramsdell, F., Brunkow, M. E., Ferguson, P. J., Whitesell, L., Kelly, T. E., Saulsbury, F. T., Chance, P. F. and Ochs, H. D., The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat. Genet. 2001. 27: 2021.
  • 3
    Brunkow, M. E., Jeffery, E. W., Hjerrild, K. A., Paeper, B., Clark, L. B., Yasayko, S.-A., Wilkinson, J. E., Galas, D., Ziegler, S. F. and Ramsdell F., Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat. Genet. 2001. 27: 6873.
  • 4
    Wildin, R. S., Ramsdell, F., Peake, J., Faravelli, F., Casanova, J.-L., Buist, N., Levy-Lahad, E., Mazzella, M., Goulet, O., Perroni, L. et al., X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat. Genet. 2001. 27: 1820.
  • 5
    Godfrey, V. L., Wilkinson, J. E. and Russell, L. B., X-linked lymphoreticular disease in the scurfy (sf) mutant mouse. Am. J. Pathol. 1991. 138: 13791387.
  • 6
    Blair, P. J., Bultman, S. J., Haas, J. C., Rouse, B. T., Wilkinson, J. E. and Godfrey, V. L., CD4+CD8 T cells are the effector cells in disease pathogenesis in the scurfy (sf) mouse. J. Immunol. 1994. 153: 37643774.
  • 7
    Tivol, E. A., Borriello, F., Schweitzer, A. N., Lynch, W. P., Bluestone, J. A. and Sharpe, A. H., Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity 1995. 3: 541547.
  • 8
    Waterhouse, P., Penninger, J. M., Timms, E., Wakeham, A., Shahinian, A., Lee, K. P., Thompson, C. B., Griesses, H. and Mak, T. W., Lymphoproliferative disorders with early lethality in mice deficient in CTLA-4. Science 1995. 270: 985988.
  • 9
    Khattri, R., Kasprowicz, D., Cox, T., Mortrud, M., Appleby, M. W., Brunkow, M. E., Ziegler, S. F. and Ramsdell, F., The amount of scurfin protein determines peripheral T cell number and responsiveness. J. Immunol. 2001. 167: 63126320.
  • 10
    Schubert, L. A., Jeffery, E., Zhang, Y., Ramsdell, F. and Ziegler, S. F., Scurfin (FOXP3) acts as a repressor of transcription and regulates T cell activation. J. Biol. Chem. 2001. 276: 3767237679.
  • 11
    Fontenot, J. D., Gavin, M. A. and Rudensky, A. Y., Foxp3 programs the development and function of CD4(+)CD25(+) regulatory T cells. Nat. Immunol. 2003. 4: 330336.
  • 12
    Hori, S., Nomura, T. and Sakaguchi, S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003. 299: 10571061.
  • 13
    Khattri, R., Cox, T., Yasayko, S.-A. and Ramsdell, F., An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat. Immunol. 2003. 4: 337342.
  • 14
    Maloy, K. J. and Powrie, F., Regulatory T cells in the control of immune pathology. Nat. Immunol. 2001. 2: 816822.
  • 15
    Sakaguchi, S., Sakaguchi, N., Shimizu, J., Yamazaki, S., Sakihama, T., Itoh, M., Kuniyasu, Y., Nomura, T., Toda, M. and Takahashi, T., Immunologic tolerance maintained by CD25+CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol. Rev. 2001. 182: 1832.
  • 16
    Gavin, M. and Rudensky, A., Control of immune homeostasis by naturally arising regulatory CD4+ T cells. Curr. Opin. Immunol. 2003. 15: 690696.
  • 17
    Piccirillo, C. A. and Shevach, E. M., Naturally-occuring CD4+CD25+ immunoregulatory T cells: central players in the arena of peripheral tolerance. Semin. Immunol. 2004. 16: 8188.
  • 18
    Thornton, A. M. and Shevach, E. M., CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J. Exp. Med. 1998. 188: 287296.
  • 19
    Jonuleit, H., Schmitt, E., Stassen, M., Tuettenberg, A., Knop, J. and Enk, A. H., Identification and functional characterization of human CD4+CD25+ T cells with regulatory properties isolated from peripheral blood. J. Exp. Med. 2001. 193: 12851294.
  • 20
    Piccirillo, C. A. and Shevach, E. M., Cutting edge: control of CD8+ T cell activation by CD4+CD25+ immunoregulatory cells. J. Immunol. 2001. 167: 11371140.
  • 21
    Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M. and Toda, M., Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 1995. 155: 11511164.
  • 22
    Read, S., Malmström, V. and Powrie, F., Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25+CD4+ regulatory T cells that control intestinal inflammation. J. Exp. Med. 2000. 192: 295302.
  • 23
    Viglietta, V., Baecher-Allan, C., Weiner, H. L. and Hafler, D. A., Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J. Exp. Med. 2004. 199: 971979.
  • 24
    Hara, M., Kingsley, C. I., Niimi, M., Read, S., Turvey, S. E., Bushell, A. R., Morris, P. J., Powrie, F. and Wood, K. J., IL-10 is required for regulatory T cells to mediate tolerance to alloantigens in vivo. J. Immunol. 2001. 166: 37893796.
  • 25
    Cohen, J. L., Trenado, A., Vasey, D., Klatzmann, D. and Salomon, B. L., CD4+CD25+ immunoregulatory T cells: new therapeutics for graft-versus-host disease. J. Exp. Med. 2002. 196: 401406.
  • 26
    Hoffmann, P., Ermann, J., Edinger, M., Fathman, C. G. and Strober, S., Donor-type CD4+CD25+ regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation. J. Exp. Med. 2002. 196: 389399.
  • 27
    Taylor, P. A., Lees, C. J. and Blazar, B. R., The infusion of ex vivo activated and expanded CD4+CD25+ immune regulatory cells inhibits graft-versus-host disease lethality. Blood 2002. 99: 34933499.
  • 28
    Curotto de Lafaille, M. A., Muriglan, S., Sunshine, M. J., Lei, Y., Kutchukhidze, N., Furtado, G. C., Wensky, A. K., Olivares-Liaalgomez, D. and Lafaille, J. J., Hyper immunolglobulin E response in mice with monoclonal populations of B and T lymphocytes. J. Exp. Med. 2001. 194: 13491359.
  • 29
    Belkaid, Y., Piccirillo, C. A., Mendez, S., Shevach, E. M. and Sacks, D. L., CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature 2002. 420: 502507.
  • 30
    Woo, E. Y., Chu, C. S., Goletz, T. J., Schlienger, K., Yeh, H., Coukos, G., Rubin, S. C., Kaiser, L. R. and June, C. H., Cutting edge: regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation. J. Immunol. 2002. 168: 42724276.
  • 31
    Liyanage, U. K., Moore, T. T., Joo, H. G., Tanaka, Y., Herrmann, V., Doherty, G., Drebin, J. A., Strasberg, S. M., Eberlein, T. J., Goedegebuure, P. S. and Linehan, D. C., Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J. Immunol. 2002. 169: 27562761.
  • 32
    Wolf, A. M., Wolf, D., Steurer, M., Gastl, G., Gunsilius, E. and Grubeck-Loebenstein, B., Increase of regulatory T cells in the peripheral blood of cancer patients. Clin. Cancer Res. 2003. 9: 606612.
  • 33
    Marshall, N. A., Christie, L. E., Munro, L. R., Culligan, D. J., Johnston, P. W., Barker, R. N. and Vickers, M. A., Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma. Blood 2004. 103: 17551762.
  • 34
    Viguier, M., Lemaître, F., Verola, O., Cho, M.-S., Gorochov, G., Dubertret, L., Bachelez, H., Kourilsky, P. and Ferradini, L., Foxp3 expressing CD4+CD25high regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells. J. Immunol. 2004. 173: 14441453.
  • 35
    Shimizu, J., Yamazaki, S. and Sakaguchi, S., Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity. J. Immunol. 1999. 163: 52115218.
  • 36
    Bruder, D., Probst-Kepper, M., Westendorf, A. M., Geffers, R., Beissert, S., Loser, K., von Boehmer, H., Buer, J. and Hansen, W., Neuropilin-1: a surface marker of regulatory T cells. Eur. J. Immunol. 2004. 34: 623630.
  • 37
    Lennon, G. G., Auffray, C., Polymeropoulos, M. and Soares, M. B., The I.M.A.G.E. Consortium: an integrated molecular analysis of genomes and their expression. Genomics 1996. 33: 151152.
  • 38
    Karube, K., Ohshima, K., Tsuchiya, T., Yamaguchi, T., Kawano, R., Suzumiya, J., Utsunomiya, A., Harada, M. and Kikuchi, M., Expression of FoxP3, a key molecule in CD4CD25 regulatory T cells, in adult T-cell leukemia/lymphoma cells. Br. J. Haematol. 2004. 126: 8184.
  • 39
    Baecher-Allan, C., Brown, J. A., Freeman, G. J. and Hafler, D. A., CD4+CD25high regulatory cells in human peripheral blood. J. Immunol. 2001. 167: 12451253.
  • 40
    Chang, C. C., Ciubotariu, R., Manavalan, J. S., Yuan, J., Colovai, A. I., Piazza, F., Lederman, S., Colonna, M., Cortesini, R., Dalla-Favera, R. and Suciu-Foca, N., Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4. Nat. Immunol. 2002. 3: 237243.
  • 41
    Najafian, N., Chitnis, T., Salama, A. D., Zhu, B., Benou, C., Yuan, X., Clarkson, M. R., Sayegh, M. H. and Khoury, S. J., Regulatory functions of CD8+CD28 T cells in an autoimmune disease model. J. Clin. Invest. 2003. 112: 10371048.
  • 42
    Liu, Z., Tugulea, S., Cortesini, R. and Suciu-Foca, N., Specific suppression of T helper alloreactivity by allo-MHC class I-restricted CD8+CD28 T cells. Int. Immunol. 1998. 10: 775783.
  • 43
    Ciubotariu, R., Colovai, A., Pennesi, G., Liu, Z., Smith, D., Berlocco, P., Cortesini, R. and Suciu-Foca, N., Specific suppression of human CD4+ Th cell responses to pig MHC antigens by CD8+CD28 regulatory T cells. J. Immunol. 1998. 161: 51935202.
  • 44
    Colovai, A., Liu, Z., Ciubotariu, R., Lederman, S., Cortesini, R. and Suciu-Foca, N., Induction of xenoreactive CD4+ T-cell anergy by suppressor CD8+CD28 T cells. Transplantation 2000. 69: 13041310.
  • 45
    Li, J., Liu, Z., Jiang, S., Cortesini, R., Lederman, S. and Suciu-Foca, N., T suppressor lymphocytes inhibit NF-κB-mediated transcription of CD86 gene in APC. J. Immunol. 1999. 163: 63866392.
  • 46
    Xystrakis, E., Dejean, A. S., Bernard, I., Druet, P., Liblau, R., Gonzalez-Dunia, D. and Sauodi, A., Identification of a novel natural regulatory CD8 T cell subset and analysis of its mechanism of regulation. Blood 2004. 104: 32943301.
  • 47
    Walker, M. R., Kasprowicz, D. J., Gersuk, V. H., Benard, A., Van Landeghen, M., Buckner, J. H. and Ziegler, S. F., Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25 T cells. J. Clin. Invest. 2003. 112: 14371443.
  • 48
    Manavalan, J. S., Kim-Schulze, S., Scotto, L., Naiyer, A. J., Vlad, G., Colombo, P. C., Marboe, C., Mancini, D., Cortesini, R. and Suciu-Foca, N., Alloantigen specific CD8+CD28 FOXP3+ T suppressor cells induce ILT3+ ILT4+ tolerogenic endothelial cells, inhibiting alloreactivity. Int. Immunol. 2004. 16: 10551068.
  • 49
    Kasprowicz, D. J., Smallwood, P. S., Tyznik, A. J. and Ziegler, S. F., Scurfin (FoxP3) controls T-dependent immune responses in vivo through regulation of CD4+ T cell effector function. J. Immunol. 2003. 171: 12161223.
  • 50
    Morgan, M. E., van Bilsen, J. H., Bakker, A. M., Heemskerk, B., Schilham, M. W., Hartgers, H. C., Elferink, B. G., van der Zanden, L., de Vries, R. R., Huizinga, T. W. et al., Expression of FOXP3 mRNA is not confined to CD4+CD25+ T regulatory cells in humans. Hum. Immunol. 2005. 66: 1320.
  • 51
    Mason, D. Y., Cordell, J. L. and Pulford, K. A. F., Production of monoclonal antibodies for immunocytochemical use. In Bullock, G. R. and Petrusz, P. (Eds.) Techniques in Immunocytochemistry. Academic Press, London 1983, pp 175216.
  • 52
    Biddolph, S. C. and Gatter, K., Immunohistochemistry of lymphoid organs. In Rowland-Jones, S. L. and McMichael, A. J. (Eds.) Lymphocytes: A Practical Approach. Oxford University Press, Oxford 2000, pp 2754.
  • 53
    Banham, A. H., Beasley, N., Campo, E., Fernandez, P. L., Fidler, C., Gatter, K., Jones, M., Mason, D. Y., Prime, J. E., Trougouboff, P. et al., The FOXP1 winged helix transcription factor is a novel candidate tumor suppressor gene on chromosome 3p. Cancer Res. 2001. 61: 88208829.
  • 54
    Banham, A. H., Connors, J. M., Brown, P. J., Cordell, J. L., Ott, G., Sreenivasan, G., Farinha, P., Horsman, D. E. and Gascoyne, R., Expression of the FOXP1 transcription factor is strongly associated with inferior survival in patients with diffuse large B-cell lymphoma. Clin. Cancer Res. 2005. 11: 10651072.
  • 55
    Erber, W. N., Pinching, A. J. and Mason, D. Y., Immunocytochemical detection of T and B cell populations in routine blood smears. Lancet 1984. 1: 10421046.
  • 56
    Marafioti, T., Jones, M., Facchetti, F., Diss, T. C., Du, M.-Q., Isaacson, P. G., Pozzobon, M., Pileri, S. A., Strickson, A., Watkins, F. and Mason, D. Y., Phenotype and genotype of interfollicular large B cells, a subpopulation of lymphocytes often with dendritic morphology. Blood 2003. 102: 28682876.
  • 57
    Dunbar, P. R., Ogg, G. S., Chen, J., Rust, N., van der Bruggen, P. and Cerundolo, V., Direct isolation, phenotyping and cloning of low-frequency antigen specific cytotoxic T lymphocytes from peripheral blood. Curr. Biol. 1998. 8: 413416.
  • 58
    Nagvekar, N., Moody, A. M., Moss, P., Roxanis, I., Curnow, J., Beeson, D., Pantic, N., Newsom-Davis, J., Vincent, A. and Willcox, N. A., A pathogenic role for the thymoma in myasthenia gravis: autosensitisation of IL4 producing T cell clones recognising extracellular acetylcholine receptor epitopes presented by minority class II isotypes. J. Clin. Invest. 1998. 101: 22682277.