Phenotypic complexity of the human regulatory T cell compartment revealed by mass cytometry

Journal of Immunology

Volumn 195, Issue 5, 2015, Pages 2030-2037

  Mason, Gavin M ^a   Lowe, Katie ^a   Melchiotti, Rossella ^b   Ellis, Richard ^b   De Rinaldis, Emanuele ^b   Peakman, Mark ^a   Heck, Susanne ^b   Lombardi, Giovanna ^a   Tree, Timothy I M ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b GUY'S AND ST THOMAS' NHS FOUNDATION TRUST   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

5' NUCLEOTIDASE; CD103 ANTIGEN; CD161 ANTIGEN; CD27 ANTIGEN; CD31 ANTIGEN; CD38 ANTIGEN; CD39 ANTIGEN; CD4 ANTIGEN; CD45RA ANTIGEN; CHEMOKINE RECEPTOR CCR4; CHEMOKINE RECEPTOR CXCR3; HLA DR ANTIGEN; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 7 RECEPTOR; L SELECTIN; BIOLOGICAL MARKER; FORKHEAD TRANSCRIPTION FACTOR; FOXP3 PROTEIN, HUMAN;

ARTICLE; CELL COMPARTMENTALIZATION; CELL POPULATION; CELLULAR IMMUNITY; CONTROLLED STUDY; CYTOMETRY; HUMAN; HUMAN CELL; IMMUNE RESPONSE; IMMUNOLOGICAL TOLERANCE; IMMUNOPHENOTYPING; IMMUNOREGULATION; LYMPHOCYTE FUNCTION; MASS CYTOMETRY; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE SUBPOPULATION; CELL CULTURE; CELL LINEAGE; CLASSIFICATION; CLUSTER ANALYSIS; FLOW CYTOMETRY; IMMUNOLOGY; METABOLISM; PROCEDURES; SINGLE CELL ANALYSIS;

BIOMARKERS; CELL LINEAGE; CELLS, CULTURED; CLUSTER ANALYSIS; FLOW CYTOMETRY; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; IMMUNOPHENOTYPING; SINGLE-CELL ANALYSIS; T-LYMPHOCYTES, REGULATORY;

EID: 84940112129     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1500703     Document Type: Article

References (48)

1. Baecher-Allan, C., V. Viglietta, and D. A. Hafler. 2004. Human CD4+CD25+ regulatory T cells. Semin. Immunol. 16: 89-98.
2. Fontenot, J. D., M. A. Gavin, and A. Y. Rudensky. 2003. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol. 4: 330-336.
3. Hori, S., T. Nomura, and S. Sakaguchi. 2003. Control of regulatory T cell development by the transcription factor Foxp3. Science 299: 1057-1061.
4. Schmidt, A., N. Oberle, and P. H. Krammer. 2012. Molecular mechanisms of treg-mediated T cell suppression. Front. Immunol. 3: 51.
5. Shevach, E. M. 2009. Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity 30: 636-645.
6. Sojka, D. K., Y. H. Huang, and D. J. Fowell. 2008. Mechanisms of regulatory T-cell suppression - a diverse arsenal for a moving target. Immunology 124: 13-22.
7. Dejaco, C., C. Duftner, B. Grubeck-Loebenstein, and M. Schirmer. 2006. Imbalance of regulatory T cells in human autoimmune diseases. Immunology 117: 289-300.
8. Long, S. A., and J. H. Buckner. 2011. CD4+FOXP3+ T regulatory cells in human autoimmunity: more than a numbers game. J. Immunol. 187: 2061-2066.
9. Marek-Trzonkowska, N., M. Mysliwiec, A. Dobyszuk, M. Grabowska, I. Techmanska, J. Juscinska, M. A. Wujtewicz, P. Witkowski, W. Mlynarski, A. Balcerska, et al. 2012. Administration of CD4+CD25highCD127- regulatory T cells preserves β-cell function in type 1 diabetes in children. Diabetes Care 35: 1817-1820.
10. Putnam, A. L., N. Safinia, A. Medvec, M. Laszkowska, M. Wray, M. A. Mintz, E. Trotta, G. L. Szot, W. Liu, A. Lares, et al. 2013. Clinical grade manufacturing of human alloantigen-reactive regulatory T cells for use in transplantation. Am. J. Transplant. 13: 3010-3020.
11. Trzonkowski, P., A. Dukat-Mazurek, M. Bieniaszewska, N. Marek- Trzonkowska, A. Dobyszuk, J. Juscinska, M. Dutka, J. Mysliwska, and A. Hellmann. 2013. Treatment of graft-versus-host disease with naturally occurring T regulatory cells. BioDrugs 27: 605-614.
12. Sugiyama, D., H. Nishikawa, Y. Maeda, M. Nishioka, A. Tanemura, I. Katayama, S. Ezoe, Y. Kanakura, E. Sato, Y. Fukumori, et al. 2013. Anti- CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking antitumor immune responses in humans. Proc. Natl. Acad. Sci. USA 110: 17945-17950.
13. Di Ianni, M., F. Falzetti, A. Carotti, A. Terenzi, F. Castellino, E. Bonifacio, B. Del Papa, T. Zei, R. I. Ostini, D. Cecchini, et al. 2011. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood 117: 3921-3928.
14. Benoist, C., and D. Mathis. 2012. Treg cells, life history, and diversity. Cold Spring Harb. Perspect. Biol. 4: a007021.
15. Miyara, M., and S. Sakaguchi. 2011. Human FoxP3(+)CD4(+) regulatory T cells: their knowns and unknowns. Immunol. Cell Biol. 89: 346-351.
16. Sakaguchi, S., M. Miyara, C. M. Costantino, and D. A. Hafler. 2010. FOXP3+ regulatory T cells in the human immune system. Nat. Rev. Immunol. 10: 490-500.
17. Miyara, M., Y. Yoshioka, A. Kitoh, T. Shima, K. Wing, A. Niwa, C. Parizot, C. Taflin, T. Heike, D. Valeyre, et al. 2009. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity 30: 899-911.
18. Ito, T., S. Hanabuchi, Y. H. Wang, W. R. Park, K. Arima, L. Bover, F. X. Qin, M. Gilliet, and Y. J. Liu. 2008. Two functional subsets of FOXP3+ regulatory T cells in human thymus and periphery. Immunity 28: 870-880.
19. Borsellino, G., M. Kleinewietfeld, D. Di Mitri, A. Sternjak, A. Diamantini, R. Giometto, S. Höpner, D. Centonze, G. Bernardi, M. L. Dell'Acqua, et al. 2007. Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood 110: 1225-1232.
20. Duhen, T., R. Duhen, A. Lanzavecchia, F. Sallusto, and D. J. Campbell. 2012. Functionally distinct subsets of human FOXP3+ Treg cells that phenotypically mirror effector Th cells. Blood 119: 4430-4440.
21. Pfoertner, S., A. Jeron, M. Probst-Kepper, C. A. Guzman, W. Hansen, A. M. Westendorf, T. Toepfer, A. J. Schrader, A. Franzke, J. Buer, and R. Geffers. 2006. Signatures of human regulatory T cells: an encounter with old friends and new players. Genome Biol. 7: R54. Available at: http://www.genomebiology.com/2006/7/7/R54.
22. Bendall, S. C., E. F. Simonds, P. Qiu, A. D. Amir, P. O. Krutzik, R. Finck, R. V. Bruggner, R. Melamed, A. Trejo, O. I. Ornatsky, et al. 2011. Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum. Science 332: 687-696.
23. Amir, el-A. D., K. L. Davis, M. D. Tadmor, E. F. Simonds, J. H. Levine, S. C. Bendall, D. K. Shenfeld, S. Krishnaswamy, G. P. Nolan, and D. Pe'er. 2013. viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia. Nat. Biotechnol. 31: 545-552.
24. Qian, Y., C. Wei, F. Eun-Hyung Lee, J. Campbell, J. Halliley, J. A. Lee, J. Cai, Y. M. Kong, E. Sadat, E. Thomson, et al. 2010. Elucidation of seventeen human peripheral blood B-cell subsets and quantification of the tetanus response using a density-based method for the automated identification of cell populations in multidimensional flow cytometry data. Cytometry B Clin. Cytom. 78(Suppl 1): S69-S82.
25. Finck, R., E. F. Simonds, A. Jager, S. Krishnaswamy, K. Sachs, W. Fantl, D. Pe'er, G. P. Nolan, and S. C. Bendall. 2013. Normalization of mass cytometry data with bead standards. Cytometry A 83: 483-494.
26. Dwyer, K. M., D. Hanidziar, P. Putheti, P. A. Hill, S. Pommey, J. L. McRae, A. Winterhalter, G. Doherty, S. Deaglio, M. Koulmanda, et al. 2010. Expression of CD39 by human peripheral blood CD4+ CD25+ T cells denotes a regulatory memory phenotype. Am. J. Transplant. 10: 2410-2420.
27. Baecher-Allan, C., E. Wolf, and D. A. Hafler. 2006. MHC class II expression identifies functionally distinct human regulatory T cells. J. Immunol. 176: 4622-4631.
28. Afzali, B., P. J. Mitchell, F. C. Edozie, G. A. Povoleri, S. E. Dowson, L. Demandt, G. Walter, J. B. Canavan, C. Scotta, B. Menon, et al. 2013. CD161 expression characterizes a subpopulation of human regulatory T cells that produces IL-17 in a STAT3-dependent manner. Eur. J. Immunol. 43: 2043-2054.
29. Pesenacker, A. M., D. Bending, S. Ursu, Q. Wu, K. Nistala, and L. R. Wedderburn. 2013. CD161 defines the subset of FoxP3+ T cells capable of producing proinflammatory cytokines. Blood 121: 2647-2658.
30. Solstad, T., S. J. Bains, J. Landskron, E. M. Aandahl, B. Thiede, K. Taskén, and K. M. Torgersen. 2011. CD147 (Basigin/Emmprin) identifies FoxP3+CD45RO+ CTLA4+-activated human regulatory T cells. Blood 118: 5141-5151.
31. Yi, H., Y. Zhen, L. Jiang, J. Zheng, and Y. Zhao. 2006. The phenotypic characterization of naturally occurring regulatory CD4+CD25+ T cells. Cell. Mol. Immunol. 3: 189-195.
32. Jago, C. B., J. Yates, N. O. Câmara, R. I. Lechler, and G. Lombardi. 2004. Differential expression of CTLA-4 among T cell subsets. Clin. Exp. Immunol. 136: 463-471.
33. Catalfamo, M., X. Tai, T. Karpova, J. McNally, and P. A. Henkart. 2008. TcRinduced regulated secretion leads to surface expression of CTLA-4 in CD4+ CD25+ T cells. Immunology 125: 70-79.
34. Deaglio, S., K. M. Dwyer, W. Gao, D. Friedman, A. Usheva, A. Erat, J. F. Chen, K. Enjyoji, J. Linden, M. Oukka, et al. 2007. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J. Exp. Med. 204: 1257-1265.
35. Afzali, B., F. C. Edozie, H. Fazekasova, C. Scottà, P. J. Mitchell, J. B. Canavan, S. Y. Kordasti, P. S. Chana, R. Ellis, G. M. Lord, et al. 2013. Comparison of regulatory T cells in hemodialysis patients and healthy controls: implications for cell therapy in transplantation. Clin. J. Am. Soc. Nephrol. 8: 1396-1405.
36. Booth, N. J., A. J. McQuaid, T. Sobande, S. Kissane, E. Agius, S. E. Jackson, M. Salmon, F. Falciani, K. Yong, M. H. Rustin, et al. 2010. Different proliferative potential and migratory characteristics of human CD4+ regulatory T cells that express either CD45RA or CD45RO. J. Immunol. 184: 4317-4326.
37. Haas, J., B. Fritzsching, P. Trübswetter, M. Korporal, L. Milkova, B. Fritz, D. Vobis, P. H. Krammer, E. Suri-Payer, and B. Wildemann. 2007. Prevalence of newly generated naive regulatory T cells (Treg) is critical for Treg suppressive function and determines Treg dysfunction in multiple sclerosis. J. Immunol. 179: 1322-1330.
38. Allakhverdi, Z., D. Fitzpatrick, A. Boisvert, N. Baba, S. Bouguermouh, M. Sarfati, and G. Delespesse. 2006. Expression of CD103 identifies human regulatory T-cell subsets. J. Allergy Clin. Immunol. 118: 1342-1349.
39. Chen, M. L., B. S. Yan, Y. Bando, V. K. Kuchroo, and H. L. Weiner. 2008. Latency-associated peptide identifies a novel CD4+CD25+ regulatory T cell subset with TGFbeta-mediated function and enhanced suppression of experimental autoimmune encephalomyelitis. J. Immunol. 180: 7327-7337.
40. Tran, D. Q., J. Andersson, D. Hardwick, L. Bebris, G. G. Illei, and E. M. Shevach. 2009. Selective expression of latency-associated peptide (LAP) and IL-1 receptor type I/II (CD121a/CD121b) on activated human FOXP3+ regulatory T cells allows for their purification from expansion cultures. Blood 113: 5125-5133.
41. Smyth, L. A., K. Ratnasothy, J. Y. Tsang, D. Boardman, A. Warley, R. Lechler, and G. Lombardi. 2013. CD73 expression on extracellular vesicles derived from CD4+ CD25+ Foxp3+ T cells contributes to their regulatory function. Eur. J. Immunol. 43: 2430-2440.
42. Sakaguchi, S., K. Wing, Y. Onishi, P. Prieto-Martin, and T. Yamaguchi. 2009. Regulatory T cells: how do they suppress immune responses? Int. Immunol. 21: 1105-1111.
43. Vignali, D. A. 2012. Mechanisms of T(reg) Suppression: Still a Long Way to Go. Front. Immunol. 3: 191.
44. Weiss, L., V. Donkova-Petrini, L. Caccavelli, M. Balbo, C. Carbonneil, and Y. Levy. 2004. Human immunodeficiency virus-driven expansion of CD4+ CD25+ regulatory T cells, which suppress HIV-specific CD4 T-cell responses in HIV-infected patients. Blood 104: 3249-3256.
45. Nadal, E., M. Garin, J. Kaeda, J. Apperley, R. Lechler, and F. Dazzi. 2007. Increased frequencies of CD4(+)CD25(high) T(regs) correlate with disease relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Leukemia 21: 472-479.
46. Noris, M., F. Casiraghi, M. Todeschini, P. Cravedi, D. Cugini, G. Monteferrante, S. Aiello, L. Cassis, E. Gotti, F. Gaspari, et al. 2007. Regulatory T cells and T cell depletion: role of immunosuppressive drugs. J. Am. Soc. Nephrol. 18: 1007-1018.
47. Ruggenenti, P., N. Perico, E. Gotti, P. Cravedi, V. D'Agati, E. Gagliardini, M. Abbate, F. Gaspari, D. Cattaneo, M. Noris, et al. 2007. Sirolimus versus cyclosporine therapy increases circulating regulatory T cells, but does not protect renal transplant patients given alemtuzumab induction from chronic allograft injury. Transplantation 84: 956-964.
48. Ahmadzadeh, M., and S. A. Rosenberg. 2006. IL-2 administration increases CD4+ CD25(hi) Foxp3+ regulatory T cells in cancer patients. Blood 107: 2409-2414.