Intrinsic TGF-β signaling promotes age-dependent CD8+ T cell polyfunctionality attrition

Journal of Clinical Investigation

Volumn 124, Issue 6, 2014, Pages 2441-2455

  Bhadra, Rajarshi ^a,b   Moretto, Magali M ^a   Castillo, Julio C ^c   Petrovas, Constantinos ^d   Ferrando Martinez, Sara ^e,f,g   Shokal, Upasana ^c   Leal, Manuel ^e   Koup, Richard A ^d   Eleftherianos, Ioannis ^c   Khan, Imtiaz A ^a  

^a GEORGE WASHINGTON UNIVERSITY SCHOOL OF MEDICINE AND HEALTH SCIENCES   (United States)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^c GEORGE WASHINGTON UNIVERSITY   (United States)

^d NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^e UNIVERSITY OF SEVILLE   (Spain)

^f HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑÓN   (Spain)

^g BIOMATERIALES Y NANOMEDICINA CIBER BBN   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA1;

AGED; AGING; ANIMAL CELL; APOPTOSIS; ARTICLE; CD8+ T LYMPHOCYTE; CELL SURVIVAL; CONTROLLED STUDY; DISEASE PREDISPOSITION; ENCEPHALITOZOON CUNICULI; IMMUNE RESPONSE; MALE; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION;

AGED; AGING; ANIMALS; ANTIGENS, CD8; APOPTOSIS; CD8-POSITIVE T-LYMPHOCYTES; CELL DIFFERENTIATION; DROSOPHILA MELANOGASTER; ENCEPHALITOZOON CUNICULI; FEMALE; HUMANS; MICE; MICE, INBRED C57BL; MICE, INBRED CBA; MICE, KNOCKOUT; MODELS, IMMUNOLOGICAL; RECEPTORS, IMMUNOLOGIC; SIGNAL TRANSDUCTION; TRANSFORMING GROWTH FACTOR BETA1;

EID: 84902145664     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI70522     Document Type: Article

References (65)

1. Nikolich-Zugich J. The aging immune system: Challenges for the 21st century. Semin Immunol. 2012;24(5):301-302.
2. Nikolich-Zugich J. T cell aging: naive but not young. J Exp Med. 2005;201(6):837-840.
3. Yager EJ, Ahmed M, Lanzer K, Randall TD, Woodland DL, Blackman MA. Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus. J Exp Med. 2008;205(3):711-723.
4. Seder RA, Darrah PA, Roederer M. T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol. 2008;8(4):247-258.
5. Precopio ML, et al. Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8 (+) T cell responses. J Exp Med. 2007;204(6):1405-1416.
6. Betts MR, et al. HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood. 2006;107(12):4781-4789.
7. Effros RB, et al. Aging and infectious diseases: workshop on HIV infection and aging: what is known and future research directions. Clin Infect Dis. 2008;47(4):542-553.
8. Didier ES, Weiss LM. Microsporidiosis: not just in AIDS patients. Curr Opin Infect Dis. 2011;24(5):490-495.
9. Lores B, Lopez-Miragaya I, Arias C, Fenoy S, Torres J, del Aguila C. Intestinal microsporidiosis due to Enterocytozoon bieneusi in elderly human immunodeficiency virus-negative patients from Vigo, Spain. Clin Infect Dis. 2002;34(7):918-921.
10. Nkinin SW, Asonganyi T, Didier ES, Kaneshiro ES. Microsporidian infection is prevalent in healthy people in Cameroon. J Clin Microbiol. 2007;45(9):2841-2846.
11. Sokolova OI, et al. Emerging microsporidian infections in Russian HIV-infected patients. J Clin Microbiol. 2011;49(6):2102-2108.
12. Mills EJ, Barnighausen T, Negin J. HIV and aging - preparing for the challenges ahead. N Engl J Med. 2012;366(14):1270-1273.
13. Balslev U, et al. Influence of age on rates of new AIDS-defining diseases and survival in 6546 AIDS patients. Scand J Infect Dis. 1997;29(4):337-343.
14. Moretto MM, Lawlor EM, Khan IA. Aging mice exhibit a functional defect in mucosal dendritic cell response against an intracellular pathogen. J Immunol. 2008;181(11):7977-7984.
15. Gigley JP, Khan IA. Plasmacytoid DC from aged mice down-regulate CD8 T cell responses by inhibiting cDC maturation after Encephalitozoon cuniculi infection. PLoS One. 2011;6(6):e20838.
16. 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.
17. Haynes L, Eaton SM, Burns EM, Randall TD, Swain SL. Newly generated CD4 T cells in aged animals do not exhibit age-related defects in response to antigen. J Exp Med. 2005;201(6):845-851.
18. Bhadra R, Gigley JP, Khan IA. The CD8 T-cell road to immunotherapy of toxoplasmosis. Immunotherapy. 2011;3(6):789-801.
19. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell. 2003;113(6):685-700.
20. Rudensky AY. Regulatory T cells and Foxp3. Immunol Rev. 2011;241(1):260-268.
21. + T cell contraction. Immunity. 2008;28(2):218-230.
22. Li MO, Flavell RA. Contextual regulation of inflammation: a duet by transforming growth factor-β and interleukin-10. Immunity. 2008;28(4):468-476.
23. Sanjabi S, Flavell RA. Overcoming the hurdles in using mouse genetic models that block TGF-β signaling. J Immunol Methods. 2010;353(1-2):111- 114.
24. Tinoco R, Alcalde V, Yang Y, Sauer K, Zuniga EI. Cell-intrinsic transforming growth factor-beta signaling mediates virus-specific CD8+ T cell deletion and viral persistence in vivo. Immunity. 2009;31(1):145-157.
25. Sanderson N, et al. Hepatic expression of mature transforming growth factor beta 1 in transgenic mice results in multiple tissue lesions. Proc Natl Acad Sci U S A. 1995;92(7):2572-2576.
26. Angelosanto JM, Wherry EJ. Transcription factor regulation of CD8+ T-cell memory and exhaustion. Immunol Rev. 2010;236:167-175.
27. Kallies A, Xin A, Belz GT, Nutt SL. Blimp-1 transcription factor is required for the differentiation of effector CD8 (+) T cells and memory responses. Immunity. 2009;31(2):283-295.
28. Rutishauser RL, et al. Transcriptional repressor Blimp-1 promotes CD8 (+) T cell terminal differentiation and represses the acquisition of central memory T cell properties. Immunity. 2009;31(2):296-308.
29. Waterfield NR, Ciche T, Clarke D. Photorhabdus and a host of hosts. Annu Rev Microbiol. 2009;63:557-574.
30. Raftery LA, Sutherland DJ. TGF-β family signal transduction in Drosophila development: from Mad to Smads. Dev Biol. 1999;210(2):251-268.
31. + T cells. Immunity. 2009;31(1):131-144.
32. Messaoudi I, Lemaoult J, Guevara-Patino JA, Metzner BM, Nikolich-Zugich J. Age-related CD8 T cell clonal expansions constrict CD8 T cell repertoire and have the potential to impair immune defense. J Exp Med. 2004;200(10):1347-1358.
33. Nikolich-Zugich J. Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections. Nat Rev Immunol. 2008;8(7):512-522.
34. + T-cell subsets during contraction of the immune response. Blood. 2008;112(9):3704-3712.
35. Waller EC, McKinney N, Hicks R, Carmichael AJ, Sissons JG, Wills MR. Differential costimulation through CD137 (4-1BB) restores proliferation of human virus-specific "effector memory" (CD28 (-) CD45RA (HI)) CD8 (+) T cells. Blood. 2007;110(13):4360-4366.
36. Andersson A, et al. IL-7 promotes CXCR3 liganddependent T cell antitumor reactivity in lung cancer. J Immunol. 2009;182(11):6951-6958.
37. Rizzo A, et al. Smad7 expression in T cells prevents colitis-associated cancer. Cancer Res. 2011;71(24):7423-7432.
38. Jung YW, Rutishauser RL, Joshi NS, Haberman AM, Kaech SM. Differential localization of effector and memory CD8 T cell subsets in lymphoid organs during acute viral infection. J Immunol. 2010;185(9):5315-5325.
39. + CTLs are essential for protective immunity against Encephalitozoon cuniculi infection. J Immunol. 1999;162(10):6086-6091.
40. Clark RI, Woodcock KJ, Geissmann F, Trouillet C, Dionne MS. Multiple TGF-β superfamily signals modulate the adult Drosophila immune response. Curr Biol. 2011;21(19):1672-1677.
41. Lawlor EM, Moretto MM, Khan IA. Optimal CD8 T-cell response against Encephalitozoon cuniculi is mediated by Toll-like receptor 4 upregulation by dendritic cells. Infect Immun. 2010;78(7):3097-3102.
42. Janssens S, Beyaert R. Role of Toll-like receptors in pathogen recognition. Clin Microbiol Rev. 2003;16(4):637-646.
43. Bouche M, Canipari R, Melchionna R, Willems D, Senni MI, Molinaro M. TGF-β autocrine loop regulates cell growth and myogenic differentiation in human rhabdomyosarcoma cells. FASEB J. 2000;14(9):1147-1158.
44. Seki E, et al. TLR4 enhances TGF-β signaling and hepatic fibrosis. Nat Med. 2007;13(11):1324-1332.
45. Rossi DJ, Jamieson CH, Weissman IL. Stems cells and the pathways to aging and cancer. Cell. 2008;132(4):681-696.
46. Chen W, Konkel JE. TGF-β and 'adaptive' Foxp3 (+) regulatory T cells. J Mol Cell Biol. 2010;2(1):30-36.
47. Oldenhove G, et al. Decrease of Foxp3+ Treg cell number and acquisition of effector cell phenotype during lethal infection. Immunity. 2009;31(5):772-786.
48. Miyazono K. Shear activates platelet-derived latent TGF-β. Blood. 2008;112(9):3533-3534.
49. Shin H, et al. A role for the transcriptional repressor Blimp-1 in CD8 (+) T cell exhaustion during chronic viral infection. Immunity. 2009;31(2):309-320.
50. Morgan MA, et al. Blimp-1/Prdm1 alternative promoter usage during mouse development and plasma cell differentiation. Mol Cell Biol. 2009;29(21):5813- 5827.
51. Arsura M, Wu M, Sonenshein GE. TGFp1 inhibits NF-KB/Rel activity inducing apoptosis of B cells: transcriptional activation of IkBcc. Immunity. 1996;5(1):31-40.
52. Dorshkind K, Montecino-Rodriguez E, Signer RA. The ageing immune system: is it ever too old to become young again? Nat Rev Immunol. 2009;9(1):57-62.
53. Yoshikawa TT. Epidemiology and unique aspects of aging and infectious diseases. Clin Infect Dis. 2000;30(6):931-933.
54. Walsh KP, Brady MT, Finlay CM, Boon L, Mills KH. Infection with a helminth parasite attenuates autoimmunity through TGF-p-mediated suppression of Th17 and Th1 responses. J Immunol. 2009;183(3):1577-1586.
55. Borkow G, Bentwich Z. HIV and helminth co-infection: is deworming necessary? Parasite Immunol. 2006;28(11):605-612.
56. Brooker S, et al. Epidemiology of plasmodiumhelminth co-infection in Africa: populations at risk, potential impact on anemia, and prospects for combining control. Am J Trop Med Hyg. 2007;77(6 suppl):88-98.
57. Mayer KD, et al. The functional heterogeneity of type 1 effector T cells in response to infection is related to the potential for IFN-y production. J Immunol. 2005;174(12):7732-7739.
58. Stetson DB, et al. Constitutive cytokine mRNAs mark natural killer (NK) and NK T cells poised for rapid effector function. J Exp Med. 2003;198(7):1069-1076.
59. Matsuda JL, et al. Mouse V alpha 14i natural killer T cells are resistant to cytokine polarization in vivo. Proc Natl Acad Sci U S A. 2003;100(14):8395-8400.
60. Ferrando-Martinez S, et al. Thymic function failure and C-reactive protein levels are independent predictors of all-cause mortality in healthy elderly humans. Age (Dordr). 2013;35(1):251-259.
61. Quezada SA, Peggs KS, Simpson TR, Shen Y, Littman DR, Allison JP. Limited tumor infiltration by activated T effector cells restricts the therapeutic activity of regulatory T cell depletion against established melanoma. The Journal of experimental medicine. 2008;205(9):2125-2138.
62. Bhadra R, Gigley JP, Weiss LM, Khan IA. Control of Toxoplasma reactivation by rescue of dysfunctional CD8+ T-cell response via PD-1-PDL-1 blockade. Proc Natl Acad Sci U S A. 2011;108(22):9196-9201.
63. Weiss LM, Vossbrinck CR. Microsporidiosis: molecular and diagnostic aspects. Adv Parasitol. 1998;40:351-395.
64. Castillo JC, Shokal U, Eleftherianos I. Immune gene transcription in Drosophila adult flies infected by entomopathogenic nematodes and their mutualistic bacteria. J Insect Physiol. 2013;59(2):179-185.
65. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2 (-Delta Delta C (T)) Method. Methods. 2001;25(4):402-408.