Immunoregulatory CD4- CD8- T cells as a potential therapeutic tool for transplantation, autoimmunity, and cancer

Frontiers in Immunology

Volumn 4, Issue JAN, 2013, Pages

  Hillhouse, Erin E ^a,b   Delisle, Jean Sébastien ^a,b   Lesage, Sylvie ^a,b  

^a UNIVERSITÉ DE MONTRÉAL   (Canada)

^b MAISONNEUVE ROSEMONT HOSPITAL   (Canada)

Author keywords

Autoimmunity; Cancer; Double negativet cells; Graft tolerance; Graft vs host disease; Immunoregulation

Indexed keywords

EID: 84874291141     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2013.00006     Document Type: Article

References (86)

1. - cell population. J. Immunol. 148, 3746-3752.
2. Baldwin, T. A., Hogquist, K. A., and Jameson, S. C. (2004). The fourth way? Harnessing aggressive tendencies in the thymus. J. Immunol. 173, 6515-6520.
3. Bleesing, J. J., Brown, M. R., Dale, J. K., Straus, S. E., Lenardo, M. J., Puck, J. M., et al. (2001a). TcR-alpha/beta(+) CD4(-)CD8(-) T cells in humans with the autoimmune lymphoproliferative syndrome express a novel CD45 isoform that is analogous to murine B220 and represents a marker of altered O-glycan biosynthesis. Clin. Immunol. 100, 314-324.
4. Bleesing, J. J., Morrow, M. R., Uzel, G., and Fleisher, T. A. (2001b). Human T cell activation induces the expression of a novel CD45 isoform that is analogous to murine B220 and is associated with altered O-glycan synthesis and onset of apoptosis. Cell. Immunol. 213, 72-81.
5. - double-negative T cells in patients with autoimmune lymphoproliferative syndrome express restricted Vbeta TCR diversity and are clonally related to CD8+ T cells. J.Immunol. 181,440-448.
6. -) alpha/beta T cell receptor-bearing cells. J. Immunol. 145, 4046-4052.
7. Chaidos, A., Patterson, S., Szydlo, R., Chaudhry, M. S., Dazzi, F., Kan-fer, E., et al. (2012). Graft invariant natural killer T-cell dose predicts risk of acute graft-versus-host disease in allogeneic hematopoietic stem cell transplantation. Blood 119,5030-5036.
8. Chao, M. P., Weissman, I. L., and Majeti, R. (2012). The CD47-SIRPalpha pathway in cancer immune evasion and potential therapeutic implications. Curr. Opin. Immunol. 24, 225-232.
9. Chen, W., Ford, M. S., Young, K. J., Cybulsky, M. I., and Zhang, L. (2003a). Role of double-negative regulatory T cells in long-term cardiac xenograft survival. J. Immunol. 170, 1846-1853.
10. Chen, W., Ford, M. S., Young, K. J., and Zhang, L. (2003b). Infusion of in vitro-generated DN T regulatory cells induces permanent cardiac allograft survival in mice. Transplant. Proc. 35, 2479-2480.
11. Chen, W., Zhou, D., Torrealba, J. R., Waddell, T. K., Grant, D., and Zhang, L. (2005). Donor lymphocyte infusion induces long-term donor-specific cardiac xenograft survival through activation of recipient double-negative regulatory T cells. J. Immunol. 175,3409-3416.
12. Cohen, P. L., and Eisenberg, R. A. (1992). The lpr and gld genes in systemic autoimmunity: life and death in the Fas lane. Immunol. Today 13, 427-428.
13. - NKT cell population. Proc. Natl. Acad. Sci. U.S.A. 105,11287-11292.
14. - T cells control intracellular bacterial infections both in vitro and in vivo. J. Exp. Med. 202, 309-319.
15. - double-negative T cells are prominent producers of IL-17A and IFN-gamma during primary respiratory murine infection with Fran-cisella tularensis live vaccine strain. J. Immunol. 184,5791-5801.
16. Crispin, J. C., Oukka, M., Bayliss, G., Cohen, R. A., Van Beek, C. A., Stillman, I. E., et al. (2008).Expanded double negative T cells in patients with systemic lupus erythe-matosus produce IL-17 and infiltrate the kidneys. J. Immunol. 181, 8761-8766.
17. + T cells and display an inflammatory effector phenotype. J. Immunol. 183,4675-4681.
18. Davidson, W. F., Dumont, F. J., Bedigian, H. G., Fowlkes, B. J., and Morse, H. C. III. (1986). Phenotypic, functional, and molecular genetic comparisons of the abnormal lymphoid cells of C3H-lpr/lpr and C3H-gld/gld mice. J. Immunol. 136, 4075-4084.
19. Del-Rey, M., Ruiz-Contreras, J., Bosque, A., Calleja, S., Gomez-Rial, J., Roldan, E., et al. (2006). A homozygous Fas ligand gene mutation in a patient causes a new type of autoimmune lymphoproliferative syndrome. Blood 108,1306-1312.
20. Di Ianni, M., Falzetti, F., Carotti, A., Terenzi, A., Castellino, F., Bonifacio, E., et al. (2011). Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood 117, 3921-3928.
21. Doreau, A., Belot, A., Bastid, J., Riche, B., Trescol-Biemont, M. C., Ranchin, B., et al. (2009). Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. Nat. Immunol. 10, 778-785.
22. Dugas, V., Beauchamp, C., Chabot-Roy, G., Hillhouse, E. E., and Lesage, S. (2010). Implication of the CD47 pathway in autoimmune diabetes. J. Autoimmun. 35, 23-32.
23. -) TCRαβ splenic cells from young NOD mice provide long-lasting protection against type 1 diabetes. PLoS ONE 5:e11427. doi: 10.1371/journal.pone.0011427
24. Fehr, T., and Sykes, M. (2004). Tolerance induction in clinical transplantation. Transpl. Immunol. 13, 117-130.
25. + CD4(-)CD8- double-negative regulatory T cells. Blood 105, 2828-2835.
26. Ford, M. S., Chen, W., Wong, S., Li, C., Vanama, R., Elford, A. R., et al. (2007). Peptide-activated double-negative T cells can prevent autoimmune type-1 diabetes development. Eur. J. Immunol. 37, 2234-2241.
27. Ford, M. S., Young, K. J., Zhang, Z., Ohashi, P. S., and Zhang, L. (2002). The immune regulatory function of lymphoproliferative double negative T cells in vitro and in vivo. J. Exp. Med. 196,261-267.
28. Ford McIntyre, M. S., Gao, J. F., Li, X., Naeini, B. M., and Zhang, L. (2011). Consequences of double negative regulatory T cell and antigen presenting cell interaction on immune response suppression. Int. Immunopharmacol. 11,597-603.
29. Ford McIntyre, M. S., Young, K. J., Gao, J., Joe, B., and Zhang, L. (2008). Cutting edge: in vivo trogocytosis as a mechanism of double negative regulatory T cell-mediated antigen-specific suppression. J. Immunol. 181, 2271-2275.
30. Gao, J. F., McIntyre, M. S., Juvet, S. C., Diao, J., Li, X., Vanama, R. B., et al. (2011). Regulation of antigen-expressing dendritic cells by double negative regulatory T cells. Eur. J. Immunol. 41,2699-2708.
31. Garza, K. M., Chan, S. M., Suri, R., Nguyen, L. T., Odermatt, B., Schoen-berger, S. P., et al. (2000). Role of antigen-presenting cells in mediating tolerance and autoimmunity. J. Exp. Med. 191,2021-2027.
32. He, K. M., Ma, Y., Wang, S., Min, W. P., Zhong, R., Jevnikar, A., et al. (2007). Donor double-negative Treg promote allogeneic mixed chimerism and tolerance. Eur. J. Immunol. 37, 3455-3466.
33. - T cells in autoimmune-prone non-obese diabetic mice. Immunol Cell Biol. 88, 771-780.
34. Hillhouse, E. E., and Lesage, S. (2012). A comprehensive review of the phe-notype and function of antigen-specific immunoregulatory double negative T cells. J. Autoimmun. doi: 10.1016/j.jaut.2012.1007.1010 [Epub ahead of print].
35. Hoffmann, P., Ermann, J., Edinger, M., Fathman, C. G., and Strober, S. (2002). Donor-type CD4(+)CD25(+) regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation.J. Exp. Med. 196,389-399.
36. Joly, E., and Hudrisier, D. (2003). What is trogocytosis and what is its purpose? Nat. Immunol. 4, 815.
37. Kishimoto, H., and Sprent, J. (1997). Negative selection in the thymus includes semimature T cells. J. Exp. Med. 185,263-271.
38. Kohrt, H. E., Pillai, A. B., Lowsky, R., and Strober, S. (2010). NKT cells, Treg, and their interactions in bone marrow transplantation. Eur. J. Immunol. 40,1862-1869.
39. Kusnierz-Glaz, C. R., Still, B. J., Amano, M., Zukor, J. D., Negrin, R. S., Blume, K. G., et al. (1997). Granulocyte colony-stimulating factor-induced comobilization of CD4- CD8- T cells and hematopoietic progenitor cells (CD34+) in the blood of normal donors. Blood 89, 2586-2595.
40. Lee, B. P., Mansfield, E., Hsieh, S. C., Hernandez-Boussard, T., Chen, W., Thomson, C. W., et al. (2005). Expression profiling of murine double-negative regulatory T cells suggest mechanisms for prolonged cardiac allograft survival. J. Immunol. 174,4535-4544.
41. Lee, S. J. (2005). New approaches for preventing and treating chronic graft-versus-host disease. Blood 105, 4200-4206.
42. Lesage, S., Charron, J., Winslow, G., and Hugo, P. (1997). Induction of thymocyte deletion by purified single peptide/major histocompatibility complex ligands. J. Immunol. 159, 2078-2081.
43. Lesage, S., Hartley, S. B., Akkaraju, S., Wilson, J., Townsend, M., and Good-now, C. C. (2002). Failure to censor forbidden clones of CD4 T cells in autoimmune diabetes. J. Exp. Med. 196,1175-1188.
44. Liyanage, U. K., Moore, T. T., Joo, H. G., Tanaka, Y., Herrmann, V., Doherty, G., et al. (2002). Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breastadenocarcinoma. J. Immunol. 169, 2756-2761.
45. Ma, Y., He, K. M., Garcia, B., Min, W., Jevnikar, A., and Zhang, Z. X. (2008). Adoptive transfer of double negative T regulatory cells induces B-cell death in vivo and alters rejection pattern of rat-to-mouse heart transplantation. Xenotransplantation 15,56-63.
46. Magerus-Chatinet, A., Stolzenberg, M. C., Loffredo, M. S., Neven, B., Schaffner, C., Ducrot, N., et al. (2009). FAS-L, IL-10, and double-negative CD4- CD8- TCR alpha/beta+ T cells are reliable markers of autoimmune lymphoprolif-erative syndrome (ALPS) associated with FAS loss of function. Blood 113, 3027-3030.
47. McIver, Z., Serio, B., Dunbar, A., O'Keefe, C. L., Powers, J., Wlodarski, M., et al. (2008). Double-negative regulatory T cells induce allotoler-ance when expanded after allogeneic haematopoietic stem cell transplantation. Br. I Haematol. 141,170-178.
48. Merims, S., Li, X., Joe, B., Dokouhaki, P., Han, M., Childs, R. W., et al. (2011). Anti-leukemia effect of ex vivo expanded DNT cells from AML patients: a potential novel autolo-gous T-cell adoptive immunotherapy. Leukemia25, 1415-1422.
49. Ohashi, P. S., Oehen, S., Buerki, K., Pircher, H., Ohashi, C. T., Oder-matt, B., et al. (1991). Ablation of "tolerance" and induction of diabetes by virus infection in viral antigen transgenic mice. Cell 65, 305-317.
50. Oldenborg, P. A. (2004). Role of CD47 in erythroid cells and in autoimmu-nity. Leuk. Lymphoma45, 1319-1327.
51. Onizuka, S., Tawara, I., Shimizu, J., Sak-aguchi, S., Fujita, T., and Nakayama, E. (1999). Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res. 59, 3128-3133.
52. Pobezinsky, L. A., Angelov, G. S., Tai, X., Jeurling, S., Van Laethem, F., Feigenbaum, L., et al. (2012). Clonal deletion and the fate of autoreac-tive thymocytes that survive negative selection. Nat. Immunol. 13, 569-578.
53. Priatel, J. J., Utting, O., and Teh, H. S. (2001). TCR/self-antigen interactions drive double-negative T cell peripheral expansion and differentiation into suppressor cells. J. Immunol. 167,6188-6194.
54. Punt, J. A., Osborne, B. A., Taka-hama, Y., Sharrow, S. O., and Singer, A. (1994). Negative selection of CD4+CD8+ thymocytes by T cell receptor-induced apoptosis requires a costimulatory signal that can be provided by CD28. J. Exp. Med. 179, 709-713.
55. Raiola, A. M., Van Lint, M. T., Val-bonesi, M., Lamparelli, T., Gualandi, E, Occhini, D., et al. (2003). Factors predicting response and graft-versus-host disease after donor lymphocyte infusions: a study on 593 infusions. Bone Marrow Transplant. 31, 687-693.
56. Rieux-Laucat, F., Le Deist, F., Hivroz, C., Roberts, I. A., Debatin, K. M., Fischer, A., et al. (1995). Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity. Science 268, 1347-1349.
57. Riol-Blanco, L., Lazarevic, V., Awasthi, A., Mitsdoerffer, M., Wilson, B. S., Croxford, A., et al. (2010). IL-23 receptor regulates unconventional IL-17-producing T cells that control bacterial infections. J. Immunol. 184, 1710-1720.
58. Rubocki, R. J., Hansen, T. H., and Lee, D. R. (1986). Molecular studies of murine mutant BALB/c-H-2dm2 define a deletion of several class I genes including the entire H-2Ld gene. Proc. Natl. Acad. Sci. U.S.A. 83, 9606-9610.
59. Sha, W C, Nelson, C. A., Newberry, R. D., Kranz, D. M., Russell, J. H., and Loh, D. Y (1988). Selective expression of an antigen receptor on CD8-bearing T lymphocytes in transgenic mice. Nature 335, 271-274.
60. Shimizu, J., Yamazaki, S., and Sakaguchi, S. (1999). Induction of tumor immunity by removing CD25+CD4+ T cells: a common basis between tumor immunity and autoimmunity. J. Immunol. 163,5211-5218.
61. Shlomchik, W. D. (2007). Graft-versus-host disease. Nat. Rev. Immunol. 7, 340-352.
62. Somasundaram, R., Jacob, L., Swo-boda, R., Caputo, L., Song, H., Basak, S., et al. (2002). Inhibition of cytolytic T lymphocyte proliferation by autologous CD4+/CD25+ regulatory T cells in a colorectal carcinoma patient is mediated by transforming growth factor-beta. Cancer Res. 62, 5267-5272.
63. - surface phe-notype and the alpha, beta het-erodimer of the T cell antigen receptor. J. Immunol. 143, 1118-1122.
64. Su, Y., Huang, X., Wang, S., Min, W P., Yin, Z., Jevnikar, A. M., etal. (2012). Double negative Treg cells promote nonmyeloablative bone marrow chimerism by inducing T-cell clonal deletion and suppressing NK cell function. Eur. J. Immunol. 42, 1216-1225.
65. Takahashi, T., Tanaka, M., Brannan, C. I., Jenkins, N. A., Copeland, N. G., Suda, T., et al. (1994). Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell 76, 969-976.
66. Thomson, C. W., Teft, W. A., Chen, W., Lee, B. P., Madrenas, J., and Zhang, L. (2006). FcR gamma presence in TCR complex of double-negative T cells is critical for their regulatory function. J. Immunol. 177, 2250-2257.
67. Tikhonova, A. N., Van Laethem, F., Hanada, K., Lu, J., Pobezinsky, L. A., Hong, C., et al. (2012). αβ T cell receptors that do not undergo major histocompatibility complex-specific thymic selection possess antibody-like recognition specificities. Immunity 36,79-91.
68. Van Laethem, F., Sarafova, S. D., Park, J. H., Tai, X., Pobezinsky, L., Guinter, T. I., et al. (2007). Deletion of CD4 and CD8 coreceptors permits generation of alphabetaT cells that recognize antigens independently of the MHC. Immunity 27, 735-750.
69. Voelkl, S., Moore, T. V., Rehli, M., Nishimura, M. I., Mackensen, A., and Fischer, K. (2009). Characterization of MHC class-I restricted TCRalphabeta+ CD4- CD8- double negative T cells recognizing the gp100 antigen from a melanoma patient after gp100 vaccination. Cancer Immunol. Immunother. 58, 709-718.
70. Watanabe-Fukunaga, R., Brannan, C. I., Copeland, N. G., Jenkins, N. A., and Nagata, S. (1992). Lymphoprolifer-ation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356, 314-317.
71. Wong, C. K., Ho, C. Y., Li, E. K., and Lam, C. W. (2000). Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) andTh2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus. Lupus 9, 589-593.
72. Yang, L., DuTemple, B., Gorczynski, R. M., Levy, G., and Zhang, L. (1999). Evidence for epitope spreading and active suppression in skin graft tolerance after donor-specific transfusion. Transplantation 67, 1404-1410.
73. Yang, L., DuTemple, B., Khan, Q., and Zhang, L. (1998). Mechanisms of long-term donor-specific allograft survival induced by pretransplant infusion of lymphocytes. Blood 91, 324-330.
74. - (double negative) T cells reconstitution in patients following hematopoietic stem-cell transplantation. Transpl. Immunol. 25,180-186.
75. Young, K. J., DuTemple, B., Phillips, M. J., and Zhang, L. (2003a). Inhibition of graft-versus-host disease by double-negative regulatory T cells. J. Immunol. 171, 134-141.
76. Young, K. J., Kay, L. S., Phillips, M. J., and Zhang, L. (2003b). Anti-tumor activity mediated by double-negative T cells. CancerRes. 63,8014-8021.
77. Young, K. J., DuTemple, B., Zhang, Z., Levy, G., and Zhang, L. (2001). CD4(-)CD8(-) regulatory T cells implicated in preventing graft-versus-host and promoting graft-versus-leukemia responses. Transplant. Proc. 33, 1762-1763.
78. Young, K. J., Yang, L., Phillips, M. J., and Zhang, L. (2002). Donor-lymphocyte infusion induces transplantation tolerance by activating systemic and graft-infiltrating double-negative regulatory T cells. Blood 100, 3408-3414.
79. Young, K. J., and Zhang, L. (2002). The nature and mechanisms of DN regulatory T-cell mediated suppression. Hum. Immunol. 63, 926-934.
80. Zeng, D., Liu, Y., Sidobre, S., Kronenberg, M., and Strober, S. (2003). Activation of natural killer T cells in NZB/W mice induces Th1-type immune responses exacerbating lupus. J. Clin. Invest. 112, 1211-1222.
81. Zhang, D., Yang, W., Degauque, N., Tian, Y., Mikita, A., and Zheng, X. X. (2007). New differentiation pathway for double-negative regulatory T cells that regulates the magnitude of immune responses. Blood 109, 4071-4079.
82. - T regulatory cells to prevent autoimmune diabetes and promote islet allograft survival in NOD mice. Diabetologia 54,2082-2092.
83. Zhang, Z. X., Lian, D., Huang, X., Wang, S., Sun, H., Liu, W., et al. (2011b). Adoptive transfer of DNT cells induces long-term cardiac allograft survival and augments recipient CD4(+)Foxp3(+) Treg cell accumulation. Transpl. Immunol. 24, 119-126.
84. Zhang, Z. X., Ma, Y., Wang, H., Arp, J., Jiang, J., Huang, X., et al. (2006). Double-negative T cells, activated by xenoantigen, lyse autologous B and T cells using a perforin/granzyme-dependent, fas-fas ligand-independent pathway. J. Immunol. 177, 6920-6929.
85. Zhang, Z. X., Stanford, W. L., and Zhang, L. (2002). Ly-6A is critical for the function of double negative regulatory T cells. Eur. J. Immunol. 32, 1584-1592.
86. Zhang, Z. X., Yang, L., Young, K. J., Dutemple, B., and Zhang, L. (2000). Identification of a previously unknown antigen-specific regulatory T cell and its mechanism of suppression. Nat Med 6, 782-789.