Autoreactive T effector memory differentiation mirrors β cell function in type 1 diabetes

Journal of Clinical Investigation

Volumn 128, Issue 8, 2018, Pages 3460-3474

  Yeo, Lorraine ^a,b   Woodwyk, Alyssa ^c   Sood, Sanjana ^b   Lorenc, Anna ^a   Eichmann, Martin ^a   Pujol Autonell, Irma ^a   Melchiotti, Rosella ^b   Skowera, Ania ^a   Fidanis, Efthymios ^b   Dolton, Garry M ^d   Tungatt, Katie ^d   Sewell, Andrew K ^d   Heck, Susanne ^b   Saxena, Alka ^b   Beam, Craig A ^c   Peakman, Mark ^a,b,e  

^a KING'S COLLEGE LONDON   (United Kingdom)

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

^c WESTERN MICHIGAN UNIVERSITY HOMER STRYKER MD SCHOOL OF MEDICINE   (United States)

^d CARDIFF UNIVERSITY SCHOOL OF MEDICINE   (United Kingdom)

^e KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

C PEPTIDE; CD16 ANTIGEN; CD57 ANTIGEN; CYTOMEGALOVIRUS ANTIGEN PP65; EPITOPE; GLUCOSE; GLUTAMATE DECARBOXYLASE 65; GRANZYME B; HLA A ANTIGEN; INSULIN; INTERLEUKIN 2; INTERLEUKIN 7 RECEPTOR; LONG ACTING INSULIN; PROTEIN; ZINC FINGER E BOX BINDING HOMEOBOX 2;

ADULT; ANTIGEN SPECIFICITY; AREA UNDER THE CURVE; ARTICLE; B LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL DIFFERENTIATION; CELL FUNCTION; CELL POPULATION; CLINICAL ARTICLE; CYTOTOXIC T LYMPHOCYTE; CYTOTOXICITY; DIET RESTRICTION; DISEASE DURATION; EFFECTOR CELL; FEMALE; FLOW CYTOMETRY; HUMAN; HUMAN CELL; IMMUNE RESPONSE; INSULIN DEPENDENT DIABETES MELLITUS; MALE; MEMORY T LYMPHOCYTE; PATIENT INFORMATION; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; RNA SEQUENCE; SELF-RENEWAL; T LYMPHOCYTE SUBPOPULATION; CHILD; CLINICAL TRIAL; CONTROLLED STUDY; IMMUNOLOGICAL MEMORY; IMMUNOLOGY; MULTICENTER STUDY; PANCREAS ISLET BETA CELL; PATHOLOGY; RANDOMIZED CONTROLLED TRIAL;

ADULT; CD8-POSITIVE T-LYMPHOCYTES; CHILD; DIABETES MELLITUS, TYPE 1; FEMALE; HUMANS; IMMUNOLOGIC MEMORY; INSULIN-SECRETING CELLS; MALE;

EID: 85051139305     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI120555     Document Type: Article

References (63)

1. Roep BO, Peakman M. Antigen targets of type 1 diabetes autoimmunity. Cold Spring Harb Perspect Med. 2012;2(4):a007781.
2. Roep BO, Peakman M. Diabetogenic T lymphocytes in human type 1 diabetes. Curr Opin Immunol. 2011;23(6):746-753.
3. Coppieters KT, et al. Demonstration of isletautoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients. J Exp Med. 2012;209(1):51-60.
4. Willcox A, Richardson SJ, Bone AJ, Foulis AK, Morgan NG. Analysis of islet inflammation in human type 1 diabetes. Clin Exp Immunol. 2009;155(2):173-181.
5. Arif S, et al. Blood and islet phenotypes indicate immunological heterogeneity in type 1 diabetes. Diabetes. 2014;63(11):3835-3845.
6. Pinkse GG, et al. Autoreactive CD8 T cells associated with beta cell destruction in type 1 diabetes. Proc Natl Acad Sci U S A. 2005;102(51):18425-18430.
7. Babon JA, et al. Analysis of self-antigen specificity of islet-infiltrating T cells from human donors with type 1 diabetes. Nat Med. 2016;22(12):1482-1487.
8. Skowera A, et al. β-Cell-specific CD8 T cell phenotype in type 1 diabetes reflects chronic autoantigen exposure. Diabetes. 2015;64(3):916-925.
9. Skowera A, et al. CTLs are targeted to kill beta cells in patients with type 1 diabetes through recognition of a glucose-regulated preproinsulin epitope. J Clin Invest. 2008;118(10):3390-3402.
10. Knight RR, et al. A distinct immunogenic region of glutamic acid decarboxylase 65 is naturally processed and presented by human islet cells to cytotoxic CD8 T cells. Clin Exp Immunol. 2015;179(1):100-107.
11. Kronenberg D, et al. Circulating preproinsulin signal peptide-specific CD8 T cells restricted by the susceptibility molecule HLA-A24 are expanded at onset of type 1 diabetes and kill β-cells. Diabetes. 2012;61(7):1752-1759.
12. Knight RR, et al. Human β-cell killing by autoreactive preproinsulin-specific CD8 T cells is predominantly granule-mediated with the potency dependent upon T-cell receptor avidity. Diabetes. 2013;62(1):205-213.
13. Greenbaum CJ, et al. Fall in C-peptide during first 2 years from diagnosis: evidence of at least two distinct phases from composite Type 1 Diabetes TrialNet data. Diabetes. 2012;61(8):2066-2073.
14. Morgan NG, Leete P, Foulis AK, Richardson SJ. Islet inflammation in human type 1 diabetes mellitus. IUBMB Life. 2014;66(11):723-734.
15. Keenan HA, et al. Residual insulin production and pancreatic β-cell turnover after 50 years of diabetes: Joslin Medalist Study. Diabetes. 2010;59(11):2846-2853.
16. Atkinson MA, Gianani R. The pancreas in human type 1 diabetes: providing new answers to ageold questions. Curr Opin Endocrinol Diabetes Obes. 2009;16(4):279-285.
17. Ogawa K, et al. A novel serum protein that is selectively produced by cytotoxic lymphocytes. J Immunol. 2001;166(10):6404-6412.
18. Peng YM, et al. Specific expression of GPR56 by human cytotoxic lymphocytes. J Leukoc Biol. 2011;90(4):735-740.
19. Bjorkstrom NK, et al. Elevated numbers of Fc gamma RIIIA+ (CD16+) effector CD8 T cells with NK cell-like function in chronic hepatitis C virus infection. J Immunol. 2008;181(6):4219-4228.
20. Clemenceau B, et al. Effector memory alphabeta T lymphocytes can express FcγRIIIa and mediate antibody-dependent cellular cytotoxicity. J Immunol. 2008;180(8):5327-5334.
21. Andrade F, Fellows E, Jenne DE, Rosen A, Young CS. Granzyme H destroys the function of critical adenoviral proteins required for viral DNA replication and granzyme B inhibition. EMBO J. 2007;26(8):2148-2157.
22. Afonina IS, Cullen SP, Martin SJ. Cytotoxic and non-cytotoxic roles of the CTL/NK protease granzyme B. Immunol Rev. 2010;235(1):105-116.
23. Wlodarski MW, et al. Phenotypic differences between healthy effector CTL and leukemic LGL cells support the notion of antigen-triggered clonal transformation in T-LGL leukemia. J Leukoc Biol. 2008;83(3):589-601.
24. Ramakrishna V, Sundarapandiyan K, Zhao B, Bylesjo M, Marsh HC, Keler T. Characterization of the human T cell response to in vitro CD27 costimulation with varlilumab. J Immunother Cancer. 2015;3:37.
25. Kaech SM, Tan JT, Wherry EJ, Konieczny BT, Surh CD, Ahmed R. Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat Immunol. 2003;4(12):1191-1198.
26. Hamann D, et al. Phenotypic and functional separation of memory and effector human CD8+ T cells. J Exp Med. 1997;186(9):1407-1418.
27. Arosa FA. CD8+CD28-T cells: certainties and uncertainties of a prevalent human T-cell subset. Immunol Cell Biol. 2002;80(1):1-13.
28. Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999;401(6754):708-712.
29. Omilusik KD, et al. Transcriptional repressor ZEB2 promotes terminal differentiation of CD8+ effector and memory T cell populations during infection. J Exp Med. 2015;212(12):2027-2039.
30. Chee J, et al. Effector-memory T cells develop in islets and report islet pathology in type 1 diabetes. J Immunol. 2014;192(2):572-580.
31. Graham KL, et al. Autoreactive cytotoxic T lymphocytes acquire higher expression of cytotoxic effector markers in the islets of NOD mice after priming in pancreatic lymph nodes. Am J Pathol. 2011;178(6):2716-2725.
32. Rigby MR, et al. Alefacept provides sustained clinical and immunological effects in newonset type 1 diabetes patients. J Clin Invest. 2015;125(8):3285-3296.
33. Appay V, et al. Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat Med. 2002;8(4):379-385.
34. Lalvani A, Brookes R, Hambleton S, Britton WJ, Hill AV, McMichael AJ. Rapid effector function in CD8+ memory T cells. J Exp Med. 1997;186(6):859-865.
35. Wherry EJ, Ahmed R. Memory CD8 T-cell differentiation during viral infection. J Virol. 2004;78(11):5535-5545.
36. Hislop AD, et al. EBV-specific CD8+ T cell memory: relationships between epitope specificity, cell phenotype, and immediate effector function. J Immunol. 2001;167(4):2019-2029.
37. Arif S, et al. β-Cell specific T-lymphocyte response has a distinct inflammatory phenotype in children with type 1 diabetes compared with adults. Diabet Med. 2017;34(3):419-425.
38. Wang EC, Taylor-Wiedeman J, Perera P, Fisher J, Borysiewicz LK. Subsets of CD8+, CD57+ cells in normal, healthy individuals: correlations with human cytomegalovirus (HCMV) carrier status, phenotypic and functional analyses. Clin Exp Immunol. 1993;94(2):297-305.
39. Labalette M, Salez F, Pruvot FR, Noel C, Dessaint JP. CD8 lymphocytosis in primary cytomegalovirus (CMV) infection of allograft recipients: expansion of an uncommon CD8+ CD57-subset and its progressive replacement by CD8+ CD57+ T cells. Clin Exp Immunol. 1994;95(3):465-471.
40. Leroy E, et al. Abnormally expanded CD8+/ Leu-7+ lymphocytes persisting in long-term bone marrow-transplanted patients are resting pre-cytotoxic T-lymphocytes. Exp Hematol. 1990;18(7):770-774.
41. Madariaga L, et al. Induction of cytolytic function in resting peripheral blood CD8+/Leu-7+ T cells through IL2/p 75 IL2-receptor interaction: a study in the allogeneic human bone marrow transplantation model. Cell Immunol. 1990;130(2):291-302.
42. Vingerhoets JH, et al. Increased cytolytic T lymphocyte activity and decreased B7 responsiveness are associated with CD28 down-regulation on CD8+ T cells from HIV-infected subjects. Clin Exp Immunol. 1995;100(3):425-433.
43. Phillips JH, Lanier LL. Lectin-dependent and anti-CD3 induced cytotoxicity are preferentially mediated by peripheral blood cytotoxic T lymphocytes expressing Leu-7 antigen. J Immunol. 1986;136(5):1579-1585.
44. Papagno L, et al. Immune activation and CD8+ T-cell differentiation towards senescence in HIV-1 infection. PLoS Biol. 2004;2(2):E20.
45. Appay V, van Lier RA, Sallusto F, Roederer M. Phenotype and function of human T lymphocyte subsets: consensus and issues. Cytometry A. 2008;73(11):975-983.
46. Mahnke YD, Brodie TM, Sallusto F, Roederer M, Lugli E. The who's who of T-cell differentiation: human memory T-cell subsets. Eur J Immunol. 2013;43(11):2797-2809.
47. Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol. 2015;15(8):486-499.
48. Brenchley JM, et al. Expression of CD57 defines replicative senescence and antigeninduced apoptotic death of CD8+ T cells. Blood. 2003;101(7):2711-2720.
49. Larbi A, Fulop T. From "truly naive" to "exhausted senescent" T cells: when markers predict functionality. Cytometry A. 2014;85(1):25-35.
50. Strioga M, Pasukoniene V, Characiejus D. CD8+ CD28-and CD8+ CD57+ T cells and their role in health and disease. Immunology. 2011;134(1):17-32.
51. McKinney EF, Lee JC, Jayne DR, Lyons PA, Smith KG. T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection. Nature. 2015;523(7562):612-616.
52. Long SA, et al. Partial exhaustion of CD8 T cells and clinical response to teplizumab in new-onset type 1 diabetes. Sci Immunol. 2016;1(5):eaai7793.
53. d'Angeac AD, Monier S, Pilling D, Travaglio-Encinoza A, Reme T, Salmon M. CD57+ T lymphocytes are derived from CD57-precursors by differentiation occurring in late immune responses. Eur J Immunol. 1994;24(7):1503-1511.
54. Pace L, et al. The epigenetic control of stemness in CD8+ T cell fate commitment. Science. 2018;359(6372):177-186.
55. Wooldridge L, et al. Interaction between the CD8 coreceptor and major histocompatibility complex class I stabilizes T cell receptor-antigen complexes at the cell surface. J Biol Chem. 2005;280(30):27491-27501.
56. Lissina A, et al. Protein kinase inhibitors substantially improve the physical detection of T-cells with peptide-MHC tetramers. J Immunol Methods. 2009;340(1):11-24.
57. Tungatt K, et al. Antibody stabilization of peptide-MHC multimers reveals functional T cells bearing extremely low-affinity TCRs. J Immunol. 2015;194(1):463-474.
58. Cernea S, Herold KC. Monitoring of antigenspecific CD8 T cells in patients with type 1 diabetes treated with antiCD3 monoclonal antibodies. Clin Immunol. 2010;134(2):121-129.
59. Luce S, et al. Single insulin-specific CD8+ T cells show characteristic gene expression profiles in human type 1 diabetes. Diabetes. 2011;60(12):3289-3299.
60. Velthuis JH, et al. Simultaneous detection of circulating autoreactive CD8+ T-cells specific for different islet cell-associated epitopes using combinatorial MHC multimers. Diabetes. 2010;59(7):1721-1730.
61. Huber W, et al. Orchestrating high-throughput genomic analysis with Bioconductor. Nat Methods. 2015;12(2):115-121.
62. Orban T, et al. Reduction in CD4 central memory T-cell subset in costimulation modulator abatacept-treated patients with recent-onset type 1 diabetes is associated with slower C-peptide decline. Diabetes. 2014;63(10):3449-3457.
63. Johnson RA, Wichern DW. Applied multivariate statistical analysis. New York, New York, USA: Pearson; 2007.