T-cell avidity and tuning: The flexible connection between tolerance and autoimmunity

International Reviews of Immunology

Volumn 25, Issue 3-4, 2006, Pages 235-258

  Van Den Boorn, Jasper ^a   Caroline Le Poole, I ^b   Luiten, Rosalie ^a  

^a UNIVERSITY OF AMSTERDAM   (Netherlands)

^b LOYOLA UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Autoimmunity; Avidity; T cell; Tolerance; Tuning

Indexed keywords

ALTERED PEPTIDE LIGAND; ANTIGEN; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; IMMUNOLOGICAL ADJUVANT; INTERLEUKIN 2; LIGAND; MELANOMA VACCINE; PEPTIDE DERIVATIVE; T LYMPHOCYTE RECEPTOR; UNCLASSIFIED DRUG;

ADOPTIVE TRANSFER; AUTOIMMUNE DISEASE; AUTOIMMUNITY; CANCER IMMUNIZATION; CELL MATURATION; CELL SELECTION; CROSS REACTION; DIABETES MELLITUS; DRUG DESIGN; HUMAN; IMMUNITY; IMMUNOLOGICAL TOLERANCE; IMMUNOREACTIVITY; IMMUNOREGULATION; IMMUNOTHERAPY; LYMPHOCYTE FUNCTION; MAJOR HISTOCOMPATIBILITY COMPLEX RESTRICTION; MELANOMA; NONHUMAN; PERIPHERAL LYMPHOCYTE; PRIORITY JOURNAL; RECEPTOR AFFINITY; REGULATORY T LYMPHOCYTE; REVIEW; T CELL DEPLETION; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; T LYMPHOCYTE AVIDITY; T LYMPHOCYTE TUNING; THYMUS; TUMOR IMMUNITY; VITILIGO;

ANIMALS; AUTOIMMUNITY; HUMANS; IMMUNE TOLERANCE; IMMUNOTHERAPY; RECEPTORS, ANTIGEN, T-CELL; T-LYMPHOCYTES;

EID: 33745821247     PISSN: 08830185     EISSN: 15635244     Source Type: Journal    
DOI: 10.1080/08830180600743081     Document Type: Review

References (90)

1. C.A. Chambers, M.S. Kuhns, J.G. Egen, and J.P. Allison, CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy, Annu. Rev. Immunol., 19: 565-594, 2001.
2. K.C. Garcia, L. Teyton, and I.A. Wilson, Structural basis of T cell recognition, Annu. Rev. Immunol., 17: 369-397, 1999.
3. P.A. van der Merwe and S.J. Davis, Molecular interactions mediating T cell antigen recognition, Annu. Rev. Immunol., 21: 659-684, 2003.
4. R.E. Toes, S.P. Schoenberger, V. van d, R. Offringa, and C.J. Melief, CD40-CD40Ligand interactions and their role in cytotoxic T lymphocyte priming and anti-tumor immunity, Semin. Immunol., 10: 443-448, 1998.
5. W.R. Heath and F.R. Carbone, Cross-presentation in viral immunity and self-tolerance, Nat. Rev. Immunol., 1: 126-134, 2001.
6. C.C. Norbury, S. Basta, K.B. Donohue, D.C. Tscharke, M.F. Princiotta, P. Berglund, J. Gibbs, J.R. Bennink, and J.W. Yewdell, CD8+ T cell cross-priming via transfer of proteasome substrates, Science, 304: 1318-1321, 2004.
7. M.C. Wolkers, N. Brouwenstijn, A.H. Bakker, M. Toebes, and T.N. Schumacher, Antigen bias in T cell cross-priming, Science, 304: 1314-1317, 2004.
8. M.L. Alegre, K.A. Frauwirth, and C.B. Thompson, T-cell regulation by CD28 and CTLA-4, Nat. Rev. Immunol., 1: 220-228, 2001.
9. J. Nikolich-Zugich, M.K. Slifka, and I. Messaoudi, The many important facets of T-cell repertoire diversity, Nat. Rev. Immunol., 4: 123-132, 2004.
10. P. Friedl, A.T. den Boer, and M. Gunzer, Tuning immune responses: Diversity and adaptation of the immunological synapse, Nat. Rev. Immunol., 5: 532-545, 2005.
11. J.B. Huppa, M. Gleimer, C. Sumen, and M.M. Davis, Continuous T cell receptor signaling required for synapse maintenance and full effector potential, Nat. Immunol., 4: 749-755, 2003.
12. D.H. Margulies, TCR avidity: It's not how strong you make it, it's how you make it strong, Nat. Immunol., 2: 669-670, 2001.
13. S.M. Anderton and D.C. Wraith, Selection and fine-tuning of the autoimmune T-cell repertoire, Nat. Rev. Immunol., 2: 487-498, 2002.
14. A.G. Cawthon and M.A. Alexander-Miller, Optimal colocalization of TCR and CD8 as a novel mechanism for the control of functional avidity, J. Immunol., 169: 3492-3498, 2002.
15. S.K. Bromley, W.R. Burack, K.G. Johnson, K. Somersalo, T.N. Sims, C. Sumen, M.M. Davis, A.S. Shaw, P.M. Allen, and M.L. Dustin, The immunological synapse, Annu. Rev. Immunol., 19: 375-396, 2001.
16. J. Jacobelli, P.G. Andres, J. Boisvert, and M.F. Krummel, New views of the immunological synapse: Variations in assembly and function, Curr. Opin. Immunol., 16: 345-352, 2004.
17. M.L. Dustin, S.K. Bromley, Z. Kan, D.A. Peterson, and E.R. Unanue, Antigen receptor engagement delivers a stop signal to migrating T lymphocytes, Proc. Natl. Acad. Sci. U. S. A., 94: 3909-3913, 1997.
18. T. Mustelin and K. Tasken, Positive and negative regulation of T-cell activation through kinases and phosphatases, Biochem. J., 371: 15-27, 2003.
19. L.E. Samelson, Signal transduction mediated by the T cell antigen receptor: The role of adapter proteins, Annu. Rev. Immunol., 20: 371-394, 2002.
20. S.C. Bunnell, V. Kapoor, R.P. Trible, W. Zhang, and L.E. Samelson, Dynamic actin polymerization drives T cell receptor-induced spreading: A role for the signal transduction adaptor LAT, Immunity, 14: 315-329, 2001.
21. M.L. Dustin and J.A. Cooper, The immunological synapse and the actin cytoskeleton: Molecular hardware for T cell signaling, Nat. Immunol., 1: 23-29, 2000.
22. M. Croft, Co-stimulatory members of the TNFR family: Keys to effective T-cell immunity? Nat. Rev. Immunol., 3: 609-620, 2003.
23. E.H. Kemp, R.A. Ajjan, E.A. Waterman, D.J. Gawkrodger, M.J. Cork, P.F. Watson, and A.P. Weetman, Analysis of a microsatellite polymorphism of the cytotoxic T-lymphocyte antigen-4 gene in patients with vitiligo, Br. J. Dermatol., 140: 73-78, 1999.
24. H. Ueda, J.M. Howson, L. Esposito, J. Heward, H. Snook, G. Chamberlain, D.B. Rainbow, K.M. Hunter, A.N. Smith, G.G. Di, M.H. Herr, I. Dahlman, F. Payne, D. Smyth, C. Lowe, R.C. Twells, S. Howlett, B. Healy, S. Nutland, H.E. Rance, V. Everett, L.J. Smink, A.C. Lam, H.J. Cordell, N.M. Walker, C. Bordin, J. Hulme, C. Motzo, F. Cucca, J.F. Hess, M.L. Metzker, J. Rogers, S. Gregory, A. Allahabadia, R. Nithiyananthan, E. Tuomilehto-Wolf, J. Tuomilehto, P. Bingley, K.M. Gillespie, D.E. Undlien, K.S. Ronningen, C. Guja, C. Ionescu-Tirgoviste, D.A. Savage, A.P. Maxwell, D.J. Carson, C.C. Patterson, J.A. Franklyn, D.G. Clayton, L.B. Peterson, L.S. Wicker, J.A. Todd, and S.C. Gough, Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease, Nature, 423: 506-511, 2003.
25. L.M. Foley, N.J. Lowe, E. Misheloff, and J.L. Tiwari, Association of HLA-DR4 with vitiligo, J. Am. Acad. Dermatol., 8: 39-40, 1983.
26. C.C. Goodnow, J. Sprent, G.B. Fazekas de St, and C.G. Vinuesa, Cellular and genetic mechanisms of self tolerance and autoimmunity, Nature, 435: 590-597, 2005.
27. M.F. Neurath, B. Weigmann, S. Finotto, J. Glickman, E. Nieuwenhuis, H. Iijima, A. Mizoguchi, E. Mizoguchi, J. Mudter, P.R. Galle, A. Bhan, F. Autschbach, B.M. Sullivan, S.J. Szabo, L.H. Glimcher, and R.S. Blumberg, The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease, J. Exp. Med., 195: 1129-1143, 2002.
28. S. Tokuhiro, R. Yamada, X. Chang, A. Suzuki, Y. Kochi, T. Sawada, M. Suzuki, M. Nagasaki, M. Ohtsuki, M. Ono, H. Furukawa, M. Nagashima, S. Yoshino, A. Mabuchi, A. Sekine, S. Saito, A. Takahashi, T. Tsunoda, Y. Nakamura, and K. Yamamoto, An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis, Nat. Genet., 35: 341-348, 2003.
29. C.L. Bennett, J. Christie, F. Ramsdell, M.E. Brunkow, P.J. Ferguson, L. Whitesell, T.E. Kelly, F.T. Saulsbury, P.F. Chance, and H.D. Ochs, The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3, Nat. Genet., 27: 20-21, 2001.
30. S.F. Ziegler, FOXP3: Of Mice and Men, Annu. Rev. Immunol., 24: 209-226, 2005.
31. E. Sebzda, S. Mariathasan, T. Ohteki, R. Jones, M.F. Bachmann, and P.S. Ohashi, Selection of the T cell repertoire, Annu. Rev. Immunol., 17: 829-874, 1999.
32. P.S. Ohashi, T-cell signalling and autoimmunity: Molecular mechanisms of disease, Nat. Rev. Immunol., 2: 427-438, 2002.
33. M.F. Bachmann, D.E. Speiser, A. Zakarian, and P.S. Ohashi, Inhibition of TCR triggering by a spectrum of altered peptide ligands suggests the mechanism for TCR antagonism, Eur. J. Immunol., 28: 3110-3119, 1998.
34. P.G. Ashton-Rickardt, A. Bandeira, J.R. Delaney, L. Van Kaer, H.P. Pircher, R.M. Zinkernagel, and S. Tonegawa, Evidence for a differential avidity model of T cell selection in the thymus, Cell, 76: 651-663, 1994.
35. E. Sebzda, V.A. Wallace, J. Mayer, R.S. Yeung, T.W. Mak, and P.S. Ohashi, Positive and negative thymocyte selection induced by different concentrations of a single peptide, Science, 263: 1615-1618, 1994.
36. K.L. Laurie, N.L. La Gruta, N. Koch, I.R. van Driel, and P.A. Gleeson, Thymic expression of a gastritogenic epitope results in positive selection of self-reactive pathogenic T cells, J. Immunol., 172: 5994-6002, 2004.
37. J.X. Gao, H. Zhang, X.F. Bai, J. Wen, X. Zheng, J. Liu, P. Zheng, and Y. Liu, Perinatal blockade of b7-1 and b7-2 inhibits clonal deletion of highly pathogenic autoreactive T cells, J. Exp. Med., 195: 959-971, 2002.
38. T.M. Laufer, J. DeKoning, J.S. Markowitz, D. Lo, and L.H. Glimcher, Unopposed positive selection and autoreactivity in mice expressing class II MHC only on thymic cortex, Nature, 383: 81-85, 1996.
39. M.S. Anderson, E.S. Venanzi, Z. Chen, S.P. Berzins, C. Benoist, and D. Mathis, The cellular mechanism of Aire control of T cell tolerance, Immunity, 23: 227-239, 2005.
40. N. Kuroda, T. Mitani, N. Takeda, N. Ishimaru, R. Arakaki, Y. Hayashi, Y. Bando, K. Izumi, T. Takahashi, T. Nomura, S. Sakaguchi, T. Ueno, Y. Takahama, D. Uchida, S. Sun, F. Kajiura, Y. Mouri, H. Han, A. Matsushima, G. Yamada, and M. Matsumoto, Development of autoimmunity against transcriptionally unrepressed target antigen in the thymus of Aire-deficient mice, J. Immunol., 174: 1862-1870, 2005.
41. G.Y. Liu, P.J. Fairchild, R.M. Smith, J.R. Prowle, D. Kioussis, and D.C. Wraith, Low avidity recognition of self-antigen by T cells permits escape from central tolerance, Immunity, 3: 407-415, 1995.
42. A.C. Anderson, L.B. Nicholson, K.L. Legge, V. Turchin, H. Zaghouani, and V.K. Kuchroo, High frequency of autoreactive myelin proteolipid protein-specific T cells in the periphery of naive mice: Mechanisms of selection of the self-reactive repertoire, J. Exp. Med., 191: 761-770, 1995.
43. V.K. Kuchroo, A.C. Anderson, H. Waldner, M. Munder, E. Bettelli, and L.B. Nicholson, T cell response in experimental autoimmune encephalomyelitis (EAE): Role of self and cross-reactive antigens in shaping, tuning, and regulating the autopathogenic T cell repertoire, Annu. Rev. Immunol., 20: 101-123, 2002.
44. D. Mason, A very high level of crossreactivity is an essential feature of the T-cell receptor, Immunol. Today, 19: 395-404, 1998.
45. D.B. Wilson, D.H. Wilson, K. Schroder, C. Pinilla, S. Blondelle, R.A. Houghten, and K.C. Garcia, Specificity and degeneracy of T cells, Mol. Immunol., 40: 1047-1055, 2004.
46. B.R. Gundlach, K.H. Wiesmuller, T. Junt, S. Kienle, G. Jung, and P. Walden, Specificity and degeneracy of minor histocompatibility antigen-specific MHC-restricted CTL, J. Immunol., 156: 3645-3651, 1996.
47. B. Hemmer, M. Vergelli, C. Pinilla, R. Houghten, and R. Martin, Probing degeneracy in T-cell recognition using peptide combinatorial libraries, Immunol. Today, 19: 163-168, 1998.
48. K. Udaka, K.H. Wiesmuller, S. Kienle, G. Jung, and P. Walden, Self-MHC-restricted peptides recognized by an alloreactive T lymphocyte clone, J. Immunol., 157: 670-678, 1996.
49. R.S. Fujinami and M.B. Oldstone, Amino acid homology between the encephalitogenic site of myelin basic protein and virus: Mechanism for autoimmunity, Science, 230: 1043-1045, 1985.
50. L.J. Albert and R.D. Inman, Molecular mimicry and autoimmunity, N. Engl. J. Med., 341: 2068-2074, 1999.
51. B.D. Evavold, J. Sloan-Lancaster, K.J. Wilson, J.B. Rothbard, and P.M. Allen, Specific T cell recognition of minimally homologous peptides: evidence for multiple endogenous ligands, Immunity, 2: 655-663, 1995.
52. M.M. Davis, J.J. Boniface, Z. Reich, D. Lyons, J. Hampl, B. Arden, and Y. Chien, Ligand recognition by alpha beta T cell receptors, Annu. Rev. Immunol., 16: 523-544, 1998.
53. S.K. Kim, M. Cornberg, X.Z. Wang, H.D. Chen, L.K. Selin, and R.M. Welsh, Private specificities of CD8 T cell responses control patterns of heterologous immunity, J. Exp. Med., 201: 523-533, 2005.
54. R.S. Fujinami and M.B. Oldstone, Molecular mimicry as a mechanism for virus-induced autoimmunity, Immunol. Res., 8: 3-15, 1989.
55. C. Benoist and D. Mathis, Autoimmunity provoked by infection: How good is the case for T cell epitope mimicry? Nat. Immunol., 2: 797-801, 2001.
56. F. Davodeau, M.A. Peyrat, F. Romagne, A. Necker, M.M. Hallet, H. Vie, and M. Bonneville, Dual T cell receptor beta chain expression on human T lymphocytes, J. Exp. Med., 181: 1391-1398, 1995.
57. R.K. Paterson, H. Bluethmann, P. Tseng, A. Dunlap, and T.H. Finkel, Development and function of autospecific dual TCR+ T lymphocytes, Int. Immunol., 11: 113-119, 1999.
58. B.H. von, J. Kirberg, and B. Rocha, An unusual lineage of alpha/beta T cells that contains autoreactive cells, J. Exp. Med., 174: 1001-1008, 1991.
59. L.A. Stephens, D. Gray, and S.M. Anderton, CD4+CD25+ regulatory T cells limit the risk of autoimmune disease arising from T cell receptor crossreactivity, Proc. Natl. Acad. Sci. U. S. A., 102: 17418-17423, 2005.
60. T.C. George, J. Bilsborough, J.L. Viney, and A.M. Norment, High antigen dose and activated dendritic cells enable Th cells to escape regulatory T cell-mediated suppression in vitro, Eur. J. Immunol., 33: 502-511, 2003.
61. C. Pasare and R. Medzhitov, Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells, Science, 299: 1033-1036, 2003.
62. P.A. Antony, C.A. Piccirillo, A. Akpinarli, S.E. Finkelstein, P.J. Speiss, D.R. Surman, D.C. Palmer, C.C. Chan, C.A. Klebanoff, W.W. Overwijk, S.A. Rosenberg, and N.P. Restifo, CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells, J. Immunol., 174: 2591-2601, 2005.
63. M.J. McGeachy, L.A. Stephens, and S.M. Anderton, Natural recovery and protection from autoimmune encephalomyelitis: contribution of CD4+CD25+ regulatory cells within the central nervous system, J. Immunol., 175: 3025-3032, 2005.
64. D.H. Busch and E.G. Pamer, T cell affinity maturation by selective expansion during infection, J. Exp. Med., 189: 701-710, 1999.
65. M.K. Slifka and J.L. Whitton, Functional avidity maturation of CD8(+) T cells without selection of higher affinity TCR, Nat. Immunol., 2: 711-717, 2001.
66. M.D. Hesse, A.Y. Karulin, B.O. Boehm, P.V. Lehmann, and M. Tary-Lehmann, A T cell clone's avidity is a function of its activation state, J. Immunol., 167: 1353-1361, 2001.
67. M.F. Bachmann, A. Gallimore, S. Linkert, V. Cerundolo, A. Lanzavecchia, M. Kopf, and A. Viola, Developmental regulation of Lck targeting to the CD8 coreceptor controls signaling in naive and memory T cells, J. Exp. Med., 189: 1521-1530, 1999.
68. S.E. Kerry, J. Buslepp, L.A. Cramer, R. Maile, L.L. Hensley, A.I. Nielsen, P. Kavathas, B.J. Vilen, E.J. Collins, and J.A. Frelinger, Interplay between TCR affinity and necessity of coreceptor ligation: high-affinity peptide-MHC/TCR interaction overcomes lack of CD8 engagement, J. Immunol., 171: 4493-4503, 2003.
69. T.M. Fahmy, J.G. Bieler, M. Edidin, and J.P. Schneck, Increased TCR avidity after T cell activation: A mechanism for sensing low-density antigen, Immunity, 14: 135-143, 2001.
70. M. Fasso, N. Anandasabapathy, F. Crawford, J. Kappler, C.G. Fathman, and W.M. Ridgway, T cell receptor (TCR)-mediated repertoire selection and loss of TCR vbeta diversity during the initiation of a CD4(+) T cell response in vivo, J. Exp. Med., 192: 1719-1730, 2000.
71. P.A. Savage, J.J. Boniface, and M.M. Davis, A kinetic basis for T cell receptor repertoire selection during an immune response, Immunity, 10: 485-492, 1999.
72. S.M. Anderton, C.G. Radu, P.A. Lowrey, E.S. Ward, and D.C. Wraith, Negative selection during the peripheral immune response to antigen, J. Exp. Med., 193: 1-11 2001.
73. A. Amrani, J. Verdaguer, P. Serra, S. Tafuro, R. Tan, and P. Santamaria, Progression of autoimmune diabetes driven by avidity maturation of a T-cell population, Nature, 406: 739-742, 2000.
74. B. Han, P. Serra, J. Yamanouchi, A. Amrani, J.F. Elliott, P. Dickie, T.P. Dilorenzo, and P. Santamaria, Developmental control of CD8 T cell-avidity maturation in autoimmune diabetes, J. Clin. Invest., 115: 1879-1887, 2005.
75. H.S. Azzam, J.B. DeJarnette, K. Huang, R. Emmons, C.S. Park, C.L. Sommers, D. El Khoury, E.W. Shores, and P.E. Love, Fine tuning of TCR signaling by CD5, J. Immunol., 166: 5464-5472, 2001.
76. E.A. Robey, F. Ramsdell, D. Kioussis, W. Sha, D. Loh, R. Axel, and B.J. Fowlkes, The level of CD8 expression can determine the outcome of thymic selection, Cell, 69: 1089-1096, 1992.
77. J.C. Zuniga-Pflucker, S.A. McCarthy, M. Weston, D.L. Longo, A. Singer, and A.M. Kruisbeek, Role of CD4 in thymocyte selection and maturation, J. Exp. Med., 169: 2085-2096, 1989.
78. M.E. Marquez, W. Ellmeier, V. Sanchez-Guajardo, A.A. Freitas, O. Acuto, and B. Di, V: CD8 T cell sensory adaptation dependent on TCR avidity for self-antigens, J. Immunol., 175: 7388-7397, 2005.
79. E. Sebzda, T.M. Kundig, C.T. Thomson, K. Aoki, S.Y. Mak, J.P. Mayer, T. Zamborelli, S.G. Nathenson, and P.S. Ohashi, Mature T cell reactivity altered by peptide agonist that induces positive selection, J. Exp. Med., 183: 1093-1104, 1996.
80. Z. Grossman and W.E. Paul, Adaptive cellular interactions in the immune system: The tunable activation threshold and the significance of subthreshold responses, Proc. Natl. Acad. Sci. U. S. A., 89: 10365-10369, 1992.
81. C. Tanchot, D.L. Barber, L. Chiodetti, and R.H. Schwartz, Adaptive tolerance of CD4+ T cells in vivo: multiple thresholds in response to a constant level of antigen presentation, J. Immunol., 167: 2030-2039, 2001.
82. N.J. Singh and R.H. Schwartz, The strength of persistent antigenic stimulation modulates adaptive tolerance in peripheral CD4+ T cells, J. Exp. Med., 198: 1107-1117, 2003.
83. S. Kissler, S.M. Anderton, and D.C. Wraith, Antigen-presenting cell activation: a link between infection and autoimmunity? J. Autoimmun., 16: 303-308, 2001.
84. B. Manoury, W.F. Gregory, R.M. Maizels, and C. Watts, Bm-CPI-2, a cystatin homolog secreted by the filarial parasite Brugia malayi, inhibits class II MHC-restricted antigen processing, Curr. Biol., 11: 447-451, 2001.
85. P. Matzinger, The danger model: a renewed sense of self, Science, 296: 301-305, 2002.
86. B. Palermo, S. Garbelli, S. Mantovani, E. Scoccia, G.A. Da Prada, P. Bernabei, M.A. Avanzini, V. Brazzelli, G. Borroni, and C. Giachino, Qualitative difference between the cytotoxic T lymphocyte responses to melanocyte antigens in melanoma and vitiligo, Eur. J. Immunol., 35: 3153-3162, 2005.
87. R.M. Luiten, E.W. Kueter, W. Mooi, M.P. Gallee, E.M. Rankin, W.R. Gerritsen, S.M. Clift, W.J. Nooijen, P. Weder, W.F. van de Kasteele, J. Sein, P.C. van den Berk, O.E. Nieweg, A.M. Berns, H. Spits, and G.C. de Gast, Immunogenicity, including vitiligo, and feasibility of vaccination with autologous GM-CSF-transduced tumor cells in metastatic melanoma patients, J. Clin. Oncol., 23: 8978-8991, 2005.
88. W.W. Overwijk, Breaking tolerance in cancer immunotherapy: Time to ACT, Curr. Opin. Immunol., 17: 187-194, 2005.
89. M.E. Dudley, J.R. Wunderlich, P.F. Robbins, J.C. Yang, P. Hwu, D.J. Schwartzentruber, S.L. Topalian, R. Sherry, N.P. Restifo, A.M. Hubicki, M.R. Robinson, M. Raffeld, P. Duray, C.A. Seipp, L. Rogers-Freezer, K.E. Morton, S.A. Mavroukakis, D.E. White, and S.A. Rosenberg, Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes, Science, 298: 850-854, 2002.
90. M.L. Fields, B.D. Hondowicz, M.H. Metzgar, S.A. Nish, G.N. Wharton, C.C. Picca, A.J. Caton, and J. Erikson CD4+ CD25+ regulatory T cells inhibit the maturation but not the initiation of an autoantibody response, J. Immunol., 175: 4255-4264, 2005.