Expanded nonhuman primate Tregs exhibit a unique gene expression signature and potently downregulate alloimmune responses

American Journal of Transplantation

Volumn 8, Issue 11, 2008, Pages 2252-2264

  Anderson, A ^a   Martens, C L ^a   Hendrix, R ^a   Stempora, L L ^a   Miller, W P ^a,b   Hamby, K ^a   Russell, M ^a   Strobert, E ^b   Blazar, B R ^c   Pearson, T C ^a   Larsen, C P ^a   Kean, L S ^a,b  

^a EMORY UNIVERSITY   (United States)

^b EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF MINNESOTA   (United States)

Author keywords

Alloimmune; Gene expression; Regulatory T cells; Rhesus

Indexed keywords

INTERLEUKIN 2; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 7 RECEPTOR;

ALLOIMMUNIZATION; ANIMAL CELL; ANTIGEN EXPRESSION; ARTICLE; CD4+ T LYMPHOCYTE; CELL CULTURE; CELL ISOLATION; CELL POPULATION; CELL PROLIFERATION; CONTROLLED STUDY; DOWN REGULATION; GENE EXPRESSION; IN VIVO STUDY; LYMPHOCYTE; MONKEY; NONHUMAN; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION;

ANIMALS; ANTIGENS, CD28; ANTIGENS, CD3; ANTIGENS, CD4; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; IMMUNOPHENOTYPING; INTERLEUKIN-2; INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT; INTERLEUKIN-7 RECEPTOR ALPHA SUBUNIT; MACACA MULATTA; MODELS, BIOLOGICAL; OLIGONUCLEOTIDE ARRAY SEQUENCE ANALYSIS; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; T-LYMPHOCYTES, REGULATORY;

EID: 53749087931     PISSN: 16006135     EISSN: 16006143     Source Type: Journal    
DOI: 10.1111/j.1600-6143.2008.02376.x     Document Type: Article

References (45)

1. Meier-Kriesche HU, Schold JD, Kaplan B. Long-term renal allograft survival: Have we made significant progress or is it time to rethink our analytic and therapeutic strategies? Am J Transplant 2004 4 : 1289 1295.
2. Newell KA, Larsen CP, Kirk AD, Newell KA, Larsen CP, Kirk AD. Transplant tolerance: Converging on a moving target. Transplantation 2006 81 : 1 6.
3. Newell KA, Larsen CP. Toward transplantation tolerance: A large step on a long road. Am J Transplant 2006 6 : 1989 1990.
4. Kean LS, Gangappa S, Pearson TC, Larsen CP. Transplant tolerance in non-human primates: Progress, current challenges and unmet needs. Am J Transplant 2006 6 (5 Pt 1 884 893.
5. Nikolich-Zugich J, Slifka MK, Messaoudi I. The many important facets of T-cell repertoire diversity. Nat Rev Immunol 2004 4 : 123 132.
6. Blattman JN, Antia R, Sourdive DJ et al. Estimating the precursor frequency of naive antigen-specific CD8 T cells. J Exp Med 2002 195 : 657 664.
7. Whitmire JK, Benning N, Whitton JL. Precursor frequency, nonlinear proliferation, and functional maturation of virus-specific CD4+ T Cells. J Immunol 2006 176 : 3028 3036.
8. Suchin EJ, Langmuir PB, Palmer E, Sayegh MH, Wells AD, Turka LA. Quantifying the frequency of alloreactive T cells in vivo: New answers to an old question. J Immunol 2001 166 : 973 981.
9. Matesic D, Valujskikh A, Pearlman E, Higgins AW, Gilliam AC, Heeger PS. Type 2 immune deviation has differential effects on alloreactive CD4+ and CD8+ T cells. J Immunol 1998 161 : 5236 5244.
10. Lindahl KF, Wilson DB. Histocompatibility antigen-activated cytotoxic T lymphocytes. II. Estimates of the frequency and specificity of precursors. J Expl Med 1977 145 : 508 522.
11. June CH, Blazar BR. Clinical application of expanded CD4 + 25+ cells. Semin Immunol 2006 18 : 78 88.
12. Kang SM, Tang Q, Bluestone JA. CD4+CD25+ regulatory T cells in transplantation: Progress, challenges and prospects. Am J Transplant 2007 7 : 1457 1463.
13. Masteller EL, Tang Q, Bluestone JA. Antigen-specific regulatory T cells-ex vivo expansion and therapeutic potential. Semin Immunol 2006 18 : 103 110.
14. Bluestone JA, Thomson AW, Shevach EM, Weiner HL. What does the future hold for cell-based tolerogenic therapy? Nat Rev Immunol 2007 7 : 650 654.
15. Tao R, Hancock WW. Regulating regulatory T cells to achieve transplant tolerance. Hepatobiliary Pancreat Dis Int 2007 6 : 348 357.
16. Oliveira V, Agua-Doce A, Duarte J, Soares MP, Graca L. Regulatory T cell maintenance of dominant tolerance: Induction of tissue self-defense? Transpl Immunol 2006 17 : 7 10.
17. Edinger M, Hoffmann P, Ermann J et al. CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med 2003 9 : 1144 1150.
18. Steiner D, Brunicki N, Bachar-Lustig E, Taylor PA, Blazar BR, Reisner Y. Overcoming T cell-mediated rejection of bone marrow allografts by T-regulatory cells: Synergism with veto cells and rapamycin. Exp Hematol 2006 34 : 802 808.
19. Steiner D, Brunicki N, Blazar BR, Bachar-Lustig E, Reisner Y. Tolerance induction by third-party "off-the-shelf" CD4+CD25+ Treg cells. Exp Hematol 2006 34 : 66 71.
20. Rezvani K, Mielke S, Ahmadzadeh M et al. High donor FOXP3-positive regulatory T-cell (Treg) content is associated with a low risk of GVHD following HLA-matched allogeneic SCT. Blood 2006 108 : 1291 1297.
21. Porter SB, Liu B, Rogosheske J et al. Suppressor function of umbilical cord blood-derived CD4+CD25+ T-regulatory cells exposed to graft-versus-host disease drugs. Transplantation 2006 82 : 23 29.
22. Torrealba JR, Katayama M, Fechner JH Jr. et al. Metastable tolerance to rhesus monkey renal transplants is correlated with allograft TGF-beta 1+CD4+ T regulatory cell infiltrates. J Immunol 2004 172 : 5753 5764.
23. Bashuda H, Kimikawa M, Seino K et al. Renal allograft rejection is prevented by adoptive transfer of anergic T cells in nonhuman primates. J Clin Invest 2005 115 : 1896 1902.
24. Judy Thomas Treg ref Gansuvd B, Asiedu CK, Goodwin J et al. In vitro expanded human CD4+CD25+ regulatory T cells suppress effector T cell proliferation. Clin Immunol 2005 115 : 3 9.
25. Ring S, Thome M, Pretsch L, Enk AH, Mahnke K. Expanded murine regulatory T cells: Analysis of phenotype and function in contact hypersensitivity reactions. J Immunol Methods 2007 326 : 10 21.
26. ΔΔC (T) method. Methods 2001 25 : 402 408.
27. Irizarry RA, Hobbs B, Collin F et al. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 2003 4 : 249 264.
28. Kean LS, Adams AB, Strobert E et al. Induction of chimerism in rhesus macaques through stem cell transplant and costimulation blockade-based immunosuppression. Am J Transplant 2007 7 : 320 335.
29. Earle KE, Tang Q, Zhou X et al. In vitro expanded human CD4+CD25+ regulatory T cells suppress effector T cell proliferation. Clin Immunol 2005 115 : 3 9.
30. Liu W, Putnam AL, Xu-Yu Z et al. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ Treg cells. J Exp Med 2006 203 : 1701 1711.
31. Hartigan-O'Connor DJ, Poon C, Sinclair E, McCune JM. Human CD4+ regulatory T cells express lower levels of the IL-7 receptor alpha chain (CD127), allowing consistent identification and sorting of live cells. J Immunol Methods 2007 319 : 41 52.
32. Koenen HJ, Fasse E, Joosten I. CD27/CFSE-based ex vivo selection of highly suppressive alloantigen-specific human regulatory T cells. J Immunol 2005 174 : 7573 7583.
33. Duggleby RC, Shaw TN, Jarvis LB, Kaur G, Gaston JS. CD27 expression discriminates between regulatory and non-regulatory cells after expansion of human peripheral blood CD4+ CD25+ cells. Immunology 2007 121 : 129 139.
34. Wick MJ, Minnerath SR, Roy S, Ramakrishnan S, Loh HH. Differential expression of opioid receptor genes in human lymphoid cell lines and peripheral blood lymphocytes. J Neuroimmunol 1996 64 : 29 36.
35. Waits PS, Purcell WM, Fulford AJ, McLeod JD. Nociceptin/orphanin FQ modulates human T cell function in vitro. J Neuroimmunol 2004 149 : 110 120.
36. Manoury B, Hewitt EW, Morrice N, Dando PM, Barrett AJ, Watts C. An asparaginyl endopeptidase processes a microbial antigen for class II MHC presentation. Nature 1998 396 : 695 699.
37. + γδ cells. J Leukocyte Biol 2006 80 : 939 952.
38. Villalobos C, Núñez L, Garcia-Sancho J. Anterior pituitary thyrotropes are multifunctional cells. Am J Physiol Endocrinol Metab 2004 287 : E1166 1170.
39. Tang Q, Bluestone JA. The Foxp3+ regulatory T cell: A jack of all trades, master of regulation. Nat Immunol 2008 9 : 239 244. Review.
40. McHugh RS, Whitters MJ, Piccirillo CA et al. CD4(+)CD25(+) immunoregulatory T cells: Gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity 2002 16 : 311 323.
41. Gavin MA, Clarke SR, Negrou E, Gallegos A, Rudensky A. Homeostasis and anergy of CD4(+)CD25(+) suppressor T cells in vivo. Nat Immunol 2002 3 : 33 41.
42. Hill JA, Feuerer M, Tash K et al. Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature. Immunity 2007 27 : 786 800.
43. Chen Z, Herman AE, Matos M, Mathis D, Benoist C. Where CD4+CD25+ Treg cells impinge on autoimmune diabetes. J Exp Med 2005 202 : 1387 1397.
44. Godfrey WR, Spoden DJ, Ge YG et al. Cord blood CD4(+)CD25(+)-derived T regulatory cell lines express FoxP3 protein and manifest potent suppressor function. Blood 2005 105 : 750 758.
45. Li L, Godfrey WR, Porter SB et al. CD4+CD25+ regulatory T-cell lines from human cord blood have functional and molecular properties of T-cell anergy. Blood 2005 106 : 3068 3073.