Homeostatic T cell proliferation as a barrier to T cell tolerance

Philosophical Transactions of the Royal Society B: Biological Sciences

Volumn 360, Issue 1461, 2005, Pages 1713-1721

  Hickman, Somia P ^a   Turka, Laurence A ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Costimulatory; Homeostasis; Memory; Proliferation; T cell; Tolerance

Indexed keywords

ANTIGEN; HOMEOSTASIS; IMMUNE SYSTEM; TOLERANCE;

BIOLOGICAL MODEL; CELL DIFFERENTIATION; CELL PROLIFERATION; HOMEOSTASIS; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOLOGY; IMMUNOTHERAPY; METHODOLOGY; REVIEW; T LYMPHOCYTE SUBPOPULATION;

CELL DIFFERENTIATION; CELL PROLIFERATION; HOMEOSTASIS; HUMANS; IMMUNE TOLERANCE; IMMUNOTHERAPY; MODELS, IMMUNOLOGICAL; T-LYMPHOCYTE SUBSETS;

EID: 33644815862     PISSN: 09628436     EISSN: None     Source Type: Journal    
DOI: 10.1098/rstb.2005.1699     Document Type: Review

References (91)

1. Adams, A. B. et al. 2003 Heterologous immunity provides a potent barrier to transplantation tolerance. J. Clin. Invest. 111, 1887-1895. (doi:10.1172/JCI200317477.)
2. Alexander-Miller, M. A., Burke, K., Koszinowski, U. H., Hansen, T. H. & Connolly, J. M. 1993 Alloreactive cytotoxic T lymphocytes generated in the presence of viral-derived peptides show exquisite peptide and MHC specificity. J. Immunol. 151, 1-10.
3. Aseffa, A., Gumy, A., Launois, P., MacDonald, H. R., Louis, J. A. & Tacchini-Cottier, F. 2002 The early IL-4 response to Leishmania major and the resulting Th2 cell maturation steering progressive disease in BALB/c mice are subject to the control of regulatory CD4+CD25+ T cells. J. Immunol. 169, 3232-3241.
4. Azzam, H. S., Grinberg, A., Lui, K., Shen, H., Shores, E. W. & Love, P. E. 1998 CD5 expression is developmentally regulated by T cell receptor (TCR) signals and TCR avidity. J. Exp. Med. 188, 2301-2311. (doi:10.1084/jem. 188.12.2301.)
5. Baid, S., Saidman, S. L., Tolkoff-Rubin, N., Williams, W. W., Delmonico, F. L., Cosimi, A. B. & Pascual, M. 2001 Managing the highly sensitized transplant recipient and B cell tolerance. Curr. Opin. Immunol. 13, 577-581. (doi:10. 1016/S0952-7915(00)00262-4.)
6. Bansal-Pakala, P., Jember, A. G. & Croft, M. 2001 Signaling through OX40 (CD134) breaks peripheral T-cell tolerance. Nat. Med. 7, 907-912. (doi:10.1038/90942.)
7. Barthlott, T., Kassiotis, G. & Stockinger, B. 2003 T cell regulation as a side effect of homeostasis and competition. J. Exp. Med. 197, 451-460. (doi:10.1084/jem.20021387.)
8. Becker, T. C., Wherry, E. J., Boone, D., Murali-Krishna, K., Antia, R., Ma, A. & Ahmed, R. 2002 Interleukin 15 is required for proliferative renewal of virus-specific memory CD8 T cells. J. Exp. Med. 195, 1541-1548. (doi:10.1084/ jem.20020369.)
9. Bensinger, S. J. et al. 2004 Distinct IL-2 receptor signaling pattern in CD4+CD25+ regulatory T cells. J. Immunol. 172, 5287-5296.
10. Bolotin, E., Annett, G., Parkman, R. & Weinberg, K. 1999 Serum levels of IL-7 in bone marrow transplant recipients: relationship to clinical characteristics and lymphocyte count. Bone Marrow Transplant. 23, 783-788. (doi:10. 1038/sj.bmt.1701655.)
11. Bruno, L., von Boehmer, H. & Kirberg, J. 1996 Cell division in the compartment of naive and memory T lymphocytes. Eur. J. Immunol. 26, 3179-3184.
12. Burchill, M. A. et al. 2003 Distinct effects of STAT5 activation on CD4+ and CD8+ T cell homeostasis: development of CD4+CD25+ regulatory T cells versus CD8+ memory T cells. J. Immunol. 171, 5853-5864.
13. Burrows, S. R., Khanna, R., Burrows, J. M. & Moss, D. J. 1994 An alloresponse in humans is dominated by cytotoxic T lymphocytes (CTL) cross-reactive with a single Epstein-Barr virus CTL epitope: implications for graft-versus-host disease. J. Exp. Med. 179, 1155-1161. (doi:10.1084/jem.179.4. 1155.)
14. Cho, B. K., Rao, V. P., Ge, Q., Eisen, H. N. & Chen, J. 2000 Homeostasis-stimulated proliferation drives naive T cells to differentiate directly into memory T cells. J. Exp. Med. 192, 549-556. (doi:10.1084/jem.192.4. 549.)
15. Cozzo, C., Larkin 3rd, J. & Caton, A. J. 2003 Cutting edge: self-peptides drive the peripheral expansion of CD4+ CD25+ regulatory T cells. J. Immunol. 171, 5678-5682.
16. Croft, M., Bradley, L. M. & Swain, S. L. 1994 Naive versus memory CD4 T cell response to antigen. Memory cells are less dependent on accessory cell costimulation and can respond to many antigen-presenting cell types including resting B cells. J. Immunol. 152, 2675-2685.
17. Dai, Z., Li, Q., Wang, Y., Gao, G., Diggs, L. S., Tellides, G. & Lakkis, F. G. 2004 CD4+CD25+ regulatory T cells suppress allograft rejection mediated by memory CD8+ T cells via a CD30-dependent mechanism. J. Clin. Invest. 113, 310-317. (doi:10.1172/JCI200419727.)
18. Davies, J. D., O'Connor, E., Hall, D., Krahl, T., Trotter, J. & Sarvetnick, N. 1999 CD4+ CD45RB low-density cells from untreated mice prevent acute allograft rejection. J. Immunol. 163, 5353-5357.
19. Dummer, W., Ernst, B., LeRoy, E., Lee, D. & Surh, C. 2001 Autologous regulation of naive T cell homeostasis within the T cell compartment. J. Immunol. 166, 2460-2468.
20. Ernst, B., Lee, D. S., Chang, J. M., Sprent, J. & Surh, C. D. 1999 The peptide ligands mediating positive selection in the thymus control T cell survival and homeostatic proliferation in the periphery. Immunity 11, 173-181. (doi:10.1016/S1074-7613(00)80092-8.)
21. Fisson, S., Darrasse-Jeze, G., Litvinova, E., Septier, F., Klatzmann, D., Liblau, R. & Salomon, B. L. 2003 Continuous activation of autoreactive CD4+CD25+ regulatory T cells in the steady state. J. Exp. Med. 198, 737-746. (doi:10.1084/jem.20030686.)
22. Forman, D., Welsh, R. M., Markees, T. G., Woda, B. A., Mordes, J. P., Rossini, A. A. & Greiner, D. L. 2002 Viral abrogation of stem cell transplantation tolerance causes graft rejection and host death by different mechanisms. J. Immunol. 168, 6047-6056.
23. Fry, T. J. et al. 2001 A potential role for interleukin-7 in T-cell homeostasis. Blood 97, 2983-2990. (doi:10.1182/blood. V97.10.2983.)
24. Gavin, M. A., Clarke, S. R., Negrou, E., Gallegos, A. & Rudensky, A. 2002 Homeostasis and anergy of CD4(+) CD25(+) suppressor T cells in vivo. Nat. Immunol. 3, 33-41. (doi:10.1038/ni743.)
25. Ge, Q., Rao, V. P., Cho, B., Eisen, H. N. & Chen, J. 2001 Dependence of lymphopenia-induced T cell proliferation on the abundance of peptide/ MHC epitopes and strength of their interaction with T cell receptors. Proc. Natl Acad. Sci. USA 98, 1728-1733. (doi:10.1073/pnas.98.4.1728.)
26. Ge, Q., Bai, A., Jones, B., Eisen, H. N. & Chen, J. 2004 Competition for self-peptide-MHC complexes and cytokines between naive and memory CD8+ T cells expressing the same or different T cell receptors. Proc. Natl Acad. Sci. USA 101, 3041-3046. (doi:10.1073/pnas. 0307339101.)
27. Gimble, J. M., Pietrangeli, C., Henley, A., Dorheim, M. A., Silver, J., Namen, A., Takeichi, M., Goridis, C. & Kincade, P. W. 1989 Characterization of murine bone marrow and spleen-derived stromal cells: analysis of leukocyte marker and growth factor mRNA transcript levels. Blood 74, 303-311.
28. Goldrath, A. W., Bogatzki, L. Y. & Bevan, M. J. 2000 Naive T cells transiently acquire a memory-like phenotype during homeostasis-driven proliferation. J. Exp. Med. 192, 557-564. (doi:10.1084/jem.192.4.557.)
29. Goldrath, A. W., Luckey, C. J., Park, R., Benoist, C. & Mathis, D. 2004 The molecular program induced in T cells undergoing homeostatic proliferation. Proc. Natl Acad. Sci. USA 101, 16885-16890. (doi:10.1073/pnas. 0407417101.)
30. Graca, L., Honey, K., Adams, E., Cobbold, S. P. & Waldmann, H. 2000 Cutting edge: anti-CD154 therapeutic antibodies induce infectious transplantation tolerance. J. Immunol. 165, 4783-4786.
31. Graca, L., Cobbold, S. P. & Waldmann, H. 2002a Identification of regulatory T cells in tolerated allografts. J. Exp. Med. 195, 1641-1646. (doi:10.1084/jem.20012097.)
32. Graca, L., Thompson, S., Lin, C. Y., Adams, E., Cobbold, S. P. & Waldmann, H. 2002b Both CD4(+)CD25(+) and CD4(+)CD25(-) regulatory cells mediate dominant transplantation tolerance. J. Immunol. 168, 5558-5565.
33. Gramaglia, I., Jember, A., Pippig, S. D., Weinberg, A. D., Killeen, N. & Croft, M. 2000 The OX40 costimulatory receptor determines the development of CD4 memory by regulating primary clonal expansion. J. Immunol. 165, 3043-3050.
34. Gudmundsdottir, H. & Turka, L. A. 2001 A closer look at homeostatic proliferation of CD4+ T cells: costimulatory requirements and role in memory formation. J. Immunol. 167, 3699-3707.
35. Hara, M., Kingsley, C. I., Niimi, M., Read, S., Turvey, S. E., Bushell, A. R., Morris, P. J., Powrie, F. & Wood, K. J. 2001 IL-10 is required for regulatory T cells to mediate tolerance to alloantigens in vivo. J. Immunol. 166, 3789-3796.
36. Heeger, P. S., Greenspan, N. S., Kuhlenschmidt, S., Dejelo, C., Hricik, D. E., Schulak, J. A. & Tary-Lehmann, M. 1999 Pretransplant frequency of donor-specific, IFN gamma-producing lymphocytes is a manifestation of immunologic memory and correlates with the risk of posttransplant rejection episodes. J. Immunol. 163, 2267-2275.
37. Hirano, A., Fraser, M. O., Jordan, M. L., Takayama, T., Lu, L. & Thomson, A. W. 2000 Graft hyporeactivity induced by donor-derived dendritic cell progenitors. Transplant. Proc. 32, 260-264. (doi:10.1016/S0041-1345(99)00951-3. )
38. Kassiotis, G., Garcia, S., Simpson, E. & Stockinger, B. 2002 Impairment of immunological memory in the absence of MHC despite survival of memory T cells. Nat. Immunol. 3, 244-250. (doi:10.1038/ni766.)
39. Kassiotis, G., Zamoyska, R. & Stockinger, B. 2003 Involvement of avidity for major histocompatibility complex in homeostasis of naive and memory T cells. J. Exp. Med. 197, 1007-1016. (doi:10.1084/jem.20021812.)
40. Kennedy, M. K. et al. 2000 Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J. Exp. Med. 191, 771-780. (doi:10.1084/ jem.191.5.771.)
41. Kieper, W. C., Prlic, M., Schmidt, C. S., Mescher, M. F. & Jameson, S. C. 2001 Il-12 enhances CD8 T cell homeostatic expansion. J. Immunol. 166, 5515-5521.
42. Kneitz, B., Herrmann, T., Yonehara, S. & Schimpl, A. 1995 Normal clonal expansion but impaired Fas-mediated cell death and anergy induction in interleukin-2-deficient mice. Eur. J. Immunol. 25, 2572-2577.
43. Koenen, H. J., Fasse, E. & Joosten, I. 2003 IL-15 and cognate antigen successfully expand de novo-induced human antigen-specific regulatory CD4+ T cells that require antigen-specific activation for suppression. J. Immunol. 171, 6431-6441.
44. Ku, C. C., Murakami, M., Sakamoto, A., Kappler, J. & Marrack, P. 2000 Control of homeostasis of CD8+ memory T cells by opposing cytokines. Science 288, 675-678. (doi:10.1126/science.288.5466.675.)
45. Kuniyasu, Y., Takahashi, T., Itoh, M., Shimizu, J., Toda, G. & Sakaguchi, S. 2000 Naturally anergic and suppressive CD25(+)CD4(+) T cells as a functionally and phenotypically distinct immunoregulatory T cell subpopulation. Int. Immunol. 12, 1145-1155. (doi:10.1093/intimm/12.8. 1145.)
46. Kupiec-Weglinski, J. W. 1996 Graft rejection in sensitized recipients. Ann. Transplant. 1, 34-40.
47. Liu, H., Hu, B., Xu, D. & Liew, F. Y. 2003 CD4+CD25+ regulatory T cells cure murine colitis: the role of IL-10, TGF-beta, and CTLA4. J. Immunol. 171, 5012-5017.
48. Lu, L. & Thomson, A. W. 2002 Manipulation of dendritic cells for tolerance induction in transplantation and autoimmune disease. Transplantation 73(Suppl. 1), 19-22. (doi:10.1097/00007890-200201151-00008.)
49. Malek, T. R., Yu, A., Vincek, V., Scibelli, P. & Kong, L. 2002 CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rbeta-deficient mice. Implications for the nonredundant function of IL-2. Immunity 17, 167-178. (doi:10.1016/ S1074-7613(02)00367-9.)
50. Markees, T. G., Phillips, N. E., Gordon, E. J., Noelle, R. J., Shultz, L. D., Mordes, J. P., Greiner, D. L. & Rossini, A. A. 1998 Long-term survival of skin allografts induced by donor splenocytes and anti-CD154 antibody in thymectomized mice requires CD4(+) T cells, interferon-gamma, and CTLA4. J. Clin. Invest. 101, 2446-2455.
51. McFarland, R. D., Douek, D. C., Koup, R. A. & Picker, L. J. 2000 Identification of a human recent thymic emigrant phenotype. Proc. Natl Acad. Sci. USA 97, 4215-4220. (doi:10.1073/pnas.070061597.)
52. Min, W. P. et al. 2003 Inhibitory feedback loop between tolerogenic dendritic cells and regulatory T cells in transplant tolerance. J. Immunol. 170, 1304-1312.
53. Mottet, C., Uhlig, H. H. & Powrie, F. 2003 Cutting edge: cure of colitis by CD4+CD25+ regulatory T cells. J. Immunol. 170, 3939-3943.
54. Murali-Krishna, K. & Ahmed, R. 2000 Cutting edge: naive T cells masquerading as memory cells. J. Immunol. 165, 1733-1737.
55. Murali-Krishna, K., Lau, L. L., Sambhara, S., Lemonnier, F., Altman, J. & Ahmed, R. 1999 Persistence of memory CD8 T cells in MHC class I-deficient mice. Science 286, 1377-1381. (doi:10.1126/science.286.5443.1377.)
56. Napolitano, L. A., Grant, R. M., Deeks, S. G., Schmidt, D., De Rosa, S. C., Herzenberg, L. A., Herndier, B. G., Andersson, J. & McCune, J. M. 2001 Increased production of IL-7 accompanies HIV-1-mediated T-cell depletion: implications for T-cell homeostasis. Nat. Med. 7, 73-79. (doi:10.1038/83381.)
57. Padovan, E., Casorati, G., Dellabona, P., Meyer, S., Brockhaus, M. & Lanzavecchia, A. 1993 Expression of two T cell receptor alpha chains: dual receptor T cells. Science 262, 422-424.
58. Padovan, E., Giachino, C., Cella, M., Valitutti, S., Acuto, O. & Lanzavecchia, A. 1995 Normal T lymphocytes can express two different T cell receptor beta chains: implications for the mechanism of allelic exclusion. J. Exp. Med. 181, 1587-1591. (doi:10.1084/jem.181.4.1587.)
59. Papiernik, M., de Moraes, M. L., Pontoux, C., Vasseur, F. & Penit, C. 1998 Regulatory CD4 T cells: expression of IL-2R alpha chain, resistance to clonal deletion and IL-2 dependency. Int. Immunol. 10, 371-378. (doi:10.1093/ intimm/10.4.371.)
60. Parker, D. C., Greiner, D. L., Phillips, N. E., Appel, M. C., Steele, A. W., Durie, F. H., Noelle, R. J., Mordes, J. P. & Rossini, A. A. 1995 Survival of mouse pancreatic islet allografts in recipients treated with allogeneic small lymphocytes and antibody to CD40 ligand. Proc. Natl Acad. Sci. USA 92, 9560-9564.
61. Pearl, J. et al. 2004a Immunocompetent memory T-cells are the dominant cell type following antibody-mediated T-cell depletion and may be a barrier to achieving tolerance. Am. J. Transplant. 4(Suppl. 8). Abstract 527
62. Pearl, J., Xu, H., Christopher, K., Leopardi, F., Preston, E., Cendales, L., Hale, D. & Kirk, A. 2004b Aggressive lymphocyte depletion does not eliminate immune memory. Am. J. Transplant. 4(Suppl. 8). Abstract 525
63. Pearson, T. 2003 Genetic disassociation of autoimmunity and resistance to costimulation blockade-induced transplantation tolerance in nonobese diabetic mice. J. Immunol. 171, 185-195.
64. Pearson, T. C., Alexander, D. Z., Winn, K. J., Linsley, P. S., Lowry, R. P. & Larsen, C. P. 1994 Transplantation tolerance induced by CTLA4-Ig. Transplantation 57, 1701-1706.
65. Ploix, C., Lo, D. & Carson, M. J. 2001 A ligand for the chemokine receptor CCR7 can influence the homeostatic proliferation of CD4 T cells and progression of autoimmunity. J. Immunol. 167, 6724-6730.
66. Qin, S., Cobbold, S. P., Pope, H., Elliott, J., Kioussis, D., Davies, J. & Waldmann, H. 1993 'Infectious' transplantation tolerance. Science 259, 974-977.
67. Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M. & Toda, M. 1995 Immunologice self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 155, 1151-1164.
68. Salomon, B., Lenschow, D. J., Rhee, L., Ashourian, N., Singh, B., Sharpe, A. & Bluestone, J. A. 2000 B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 12, 431-440. (doi:10. 1016/S1074-7613(00)80195-8.)
69. Schluns, K. S., Kieper, W. C., Jameson, S. C. & Lefrancois, L. 2000 Interleukin-7 mediates the homeostasis of naive and memory CD8 T cells in vivo. Nat. Immunol. 1, 426-432. (doi:10.1038/80868.)
70. Shimizu, J., Yamazaki, S. & 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.
71. Singh, B., Read, S., Asseman, C., Malmstrom, V., Mottet, C., Stephens, L. A., Stepankova, R., Tlaskalova, H. & Powrie, F. 2001 Control of intestinal inflammation by regulatory T cells. Immunol. Rev. 182, 190-200. (doi:10. 1034/j.1600-065X.2001.1820115.x.)
72. Smith, K., Seddon, B., Purbhoo, M. A., Zamoyska, R., Fisher, A. G. & Merkenschlager, M. 2001 Sensory adaptation in naive peripheral CD4 T cells. J. Exp. Med. 194, 1253-1261. (doi:10.1084/jem.194.9.1253.)
73. Steinman, R. M., Hawiger, D. & Nussenzweig, M. C. 2003 Tolerogenic dendritic cells. Annu. Rev. Immunol. 21, 685-711. (doi:10.1146/annurev.immunol. 21.120601. 141040.)
74. Surh, C. D. & Sprent, J. 2000 Homeostatic T cell proliferation: how far can T cells be activated to self-ligands? J. Exp. Med. 192, F9-F14. (doi:10.1084/jem. 192.4.F9.)
75. Swain, S. L., Croft, M., Dubey, C., Haynes, L., Rogers, P., Zhang, X. & Bradley, L. M. 1996 From naive to memory T cells. Immunol. Rev. 150, 143-167.
76. Takeda, I., Ine, S., Killeen, N., Ndhlovu, L. C., Murata, K., Satomi, S., Sugamura, K. & Ishii, N. 2004 Distinct roles for the OX40-OX40 ligand interaction in regulatory and nonregulatory T cells. J. Immunol. 172, 3580-3589.
77. Tan, J. T., Ernst, B., Kieper, W. C., LeRoy, E., Sprent, J. & Surh, C. D. 2002 Interleukin (IL)-15 and IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+ cells but are not required for memory phenotype CD4+ cells. J. Exp. Med. 195, 1523-1532. (doi:10.1084/ jem.20020066.)
78. Tang, Q., Henriksen, K. J., Boden, E. K., Tooley, A. J., Ye, J., Subudhi, S. K., Zheng, X. X., Strom, T. B. & Bluestone, J. A. 2003 Cutting edge: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells. J. Immunol. 171, 3348-3352.
79. Thornton, A. M. & Shevach, E. M. 2000 Suppressor effector function of CD4+CD25+ immunoregulatory T cells is antigen nonspecific. J. Immunol. 164, 183-190.
80. Tittle, T. V., Weinberg, A. D., Steinkeler, C. N. & Maziarz, R. T. 1997 Expression of the T-cell activation antigen, OX-40, identifies alloreactive T cells in acute graft versus-host disease. Blood 89, 4652-4658.
81. Tough, D. F. & Sprent, J. 1994 Turnover of naive- and memory-phenotype T cells. J. Exp. Med. 179, 1127-1135. (doi:10.1084/jem.179.4. 1127.)
82. Walker, L. S. & Abbas, A. K. 2002 The enemy within: keeping self-reactive T cells at bay in the periphery. Nat. Rev. Immunol. 2, 11-19. (doi:10.1038/nri701.)
83. Wang, Q., Strong, J. & Killeen, N. 2001 Homeostatic competition among T cells revealed by conditional inactivation of the mouse Cd4 gene. J. Exp. Med. 194, 1721-1730. (doi:10.1084/jem.194.12.1721.)
84. Welsh, R. M., Markees, T. G., Woda, B. A., Daniels, K. A., Brehm, M. A., Mordes, J. P., Greiner, D. L. & Rossini, A. A. 2000 Virus-induced abrogation of transplantation tolerance induced by donor-specific transfusion and anti-CD154 antibody. J. Virol. 74, 2210-2218. (doi:10.1128/ JVI.74.5.2210-2218. 2000.)
85. Williams, M. A. et al. 2001 Characterization of virus-mediated inhibition of mixed chimerism and allospecific tolerance. J Immunol. 167, 4987-4995.
86. Williams, M. A., Onami, T. M., Adams, A. B., Durham, M. M., Pearson, T. C., Ahmed, R. & Larsen, C. P. 2002 Cutting edge: persistent viral infection prevents tolerance induction and escapes immune control following CD28/CD40 blockade-based regimen. J. Immunol. 169, 5387-5391.
87. Woo, E. Y., Chu, C. S., Goletz, T. J., Schlienger, K., Yeh, H., Coukos, G., Rubin, S. C., Kaiser, L. R. & June, C. H. 2001 Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res. 61, 4766-4772.
88. Woo, E. Y., Yeh, H., Chu, C. S., Schlienger, K., Carroll, R. G., Riley, J. L., Kaiser, L. R. & June, C. H. 2002 Cutting edge: regulatory T cells from lung cancer patients directly inhibit autologous T cell proliferation. J. Immunol. 168, 4272-4276.
89. Wu, Z. et al. 2004 Homeostatic proliferation is a barrier to transplantation tolerance. Nat. Med. 10, 87-92. (doi:10. 1038/nm965.)
90. Xu, D., Liu, H., Komai-Koma, M., Campbell, C., McSharry, C., Alexander, J. & Liew, F. Y. 2003 CD4+CD25+ regulatory T cells suppress differentiation and functions of Th1 and Th2 cells. Leishmania major infection, and colitis in mice. J. Immunol. 170, 394-399.
91. Zheng, X. X., Sanchez-Fueyo, A., Sho, M., Domenig, C., Sayegh, M. H. & Strom, T. B. 2003 Favorably tipping the balance between cytopathic and regulatory T cells to create transplantation tolerance. Immunity 19, 503-514. (doi:10.1016/S1074-7613(03)00259-0.)