The Timing of Stimulation and IL-2 Signaling Regulate Secondary CD8 T Cell Responses
Since memory CD8 T cells afford hosts increased protection, extensive research has been devoted to understanding the parameters that affect the generation of these cells. Humans are typically infected with pathogens more than once, thus leading to re-stimulation of existing primary memory CD8 T cell populations. The factors influencing the development of CD8 T cells responding to repetitive antigen stimulations remain unknown. We demonstrate that the time at which primary memory CD8 T cells encounter antigen and are re-stimulated during infection influences the outcome of a secondary pathogen-specific CD8 T cell response. We show that at the time of antigen re-encounter, interleukin-2 cytokine signals received by developing secondary CD8 T cells impact the rate of acquiring secondary memory CD8 T cell characteristics. These data indicate that secondary memory CD8 T cell generation is a process that can be manipulated, which may have implications in the development of consecutive prime-boost immunization strategies.
Vyšlo v časopise:
The Timing of Stimulation and IL-2 Signaling Regulate Secondary CD8 T Cell Responses. PLoS Pathog 11(10): e32767. doi:10.1371/journal.ppat.1005199
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1005199
Souhrn
Since memory CD8 T cells afford hosts increased protection, extensive research has been devoted to understanding the parameters that affect the generation of these cells. Humans are typically infected with pathogens more than once, thus leading to re-stimulation of existing primary memory CD8 T cell populations. The factors influencing the development of CD8 T cells responding to repetitive antigen stimulations remain unknown. We demonstrate that the time at which primary memory CD8 T cells encounter antigen and are re-stimulated during infection influences the outcome of a secondary pathogen-specific CD8 T cell response. We show that at the time of antigen re-encounter, interleukin-2 cytokine signals received by developing secondary CD8 T cells impact the rate of acquiring secondary memory CD8 T cell characteristics. These data indicate that secondary memory CD8 T cell generation is a process that can be manipulated, which may have implications in the development of consecutive prime-boost immunization strategies.
Zdroje
1. Badovinac VP, Harty JT (2006) Programming, demarcating, and manipulating CD8+ T-cell memory. Immunol Rev 211: 67–80. 16824118
2. Harty JT, Badovinac VP (2008) Shaping and reshaping CD8+ T-cell memory. Nat Rev Immunol 8: 107–119. doi: 10.1038/nri2251 18219309
3. Kaech SM, Wherry EJ, Ahmed R (2002) Effector and memory T-cell differentiation: implications for vaccine development. Nat Rev Immunol 2: 251–262. 12001996
4. Sallusto F, Lanzavecchia A, Araki K, Ahmed R (2010) From vaccines to memory and back. Immunity 33: 451–463. doi: 10.1016/j.immuni.2010.10.008 21029957
5. Seder RA, Darrah PA, Roederer M (2008) T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol 8: 247–258. doi: 10.1038/nri2274 18323851
6. Butler NS, Nolz JC, Harty JT (2011) Immunologic considerations for generating memory CD8 T cells through vaccination. Cell Microbiol 13: 925–933. doi: 10.1111/j.1462-5822.2011.01594.x 21501363
7. Lefrancois L (2006) Development, trafficking, and function of memory T-cell subsets. Immunol Rev 211: 93–103. 16824120
8. Badovinac VP, Porter BB, Harty JT (2002) Programmed contraction of CD8(+) T cells after infection. Nat Immunol 3: 619–626. 12055624
9. Jameson SC, Masopust D (2009) Diversity in T cell memory: an embarrassment of riches. Immunity 31: 859–871. doi: 10.1016/j.immuni.2009.11.007 20064446
10. Kaech SM, Wherry EJ (2007) Heterogeneity and cell-fate decisions in effector and memory CD8+ T cell differentiation during viral infection. Immunity 27: 393–405. 17892848
11. Mescher MF, Curtsinger JM, Agarwal P, Casey KA, Gerner M, et al. (2006) Signals required for programming effector and memory development by CD8+ T cells. Immunol Rev 211: 81–92. 16824119
12. Haring JS, Badovinac VP, Harty JT (2006) Inflaming the CD8+ T cell response. Immunity 25: 19–29. 16860754
13. Williams MA, Bevan MJ (2007) Effector and memory CTL differentiation. Annu Rev Immunol 25: 171–192. 17129182
14. Butz EA, Bevan MJ (1998) Massive expansion of antigen-specific CD8+ T cells during an acute virus infection. Immunity 8: 167–175. 9491998
15. Doherty PC (1998) The numbers game for virus-specific CD8+ T cells. Science 280: 227. 9565533
16. Badovinac VP, Harty JT (2007) Manipulating the rate of memory CD8+ T cell generation after acute infection. J Immunol 179: 53–63. 17579021
17. Badovinac VP, Messingham KA, Jabbari A, Haring JS, Harty JT (2005) Accelerated CD8+ T-cell memory and prime-boost response after dendritic-cell vaccination. Nat Med 11: 748–756. 15951824
18. Pham NL, Badovinac VP, Harty JT (2009) A default pathway of memory CD8 T cell differentiation after dendritic cell immunization is deflected by encounter with inflammatory cytokines during antigen-driven proliferation. J Immunol 183: 2337–2348. doi: 10.4049/jimmunol.0901203 19635915
19. Pham NL, Pewe LL, Fleenor CJ, Langlois RA, Legge KL, et al. (2010) Exploiting cross-priming to generate protective CD8 T-cell immunity rapidly. Proc Natl Acad Sci U S A 107: 12198–12203. doi: 10.1073/pnas.1004661107 20616089
20. Badovinac VP, Porter BB, Harty JT (2004) CD8+ T cell contraction is controlled by early inflammation. Nat Immunol 5: 809–817. 15247915
21. Mercado R, Vijh S, Allen SE, Kerksiek K, Pilip IM, et al. (2000) Early programming of T cell populations responding to bacterial infection. J Immunol 165: 6833–6839. 11120806
22. Martin MD, Wirth TC, Lauer P, Harty JT, Badovinac VP (2011) The impact of pre-existing memory on differentiation of newly recruited naive CD8 T cells. J Immunol 187: 2923–2931. doi: 10.4049/jimmunol.1100698 21832161
23. D'Souza WN, Hedrick SM (2006) Cutting edge: latecomer CD8 T cells are imprinted with a unique differentiation program. J Immunol 177: 777–781. 16818730
24. Fousteri G, Dave A, Juedes A, Juntti T, Morin B, et al. (2011) Increased memory conversion of naive CD8 T cells activated during late phases of acute virus infection due to decreased cumulative antigen exposure. PLoS One 6: e14502. doi: 10.1371/journal.pone.0014502 21253594
25. Nolz JC, Harty JT (2011) Strategies and implications for prime-boost vaccination to generate memory CD8 T cells. Adv Exp Med Biol 780: 69–83. doi: 10.1007/978-1-4419-5632-3_7 21842366
26. Woodland DL (2004) Jump-starting the immune system: prime-boosting comes of age. Trends Immunol 25: 98–104. 15102369
27. Wirth TC, Xue HH, Rai D, Sabel JT, Bair T, et al. (2010) Repetitive antigen stimulation induces stepwise transcriptome diversification but preserves a core signature of memory CD8(+) T cell differentiation. Immunity 33: 128–140. doi: 10.1016/j.immuni.2010.06.014 20619696
28. Wirth TC, Harty JT, Badovinac VP (2010) Modulating numbers and phenotype of CD8+ T cells in secondary immune responses. Eur J Immunol 40: 1916–1926. doi: 10.1002/eji.201040310 20411564
29. Wirth TC, Martin MD, Starbeck-Miller G, Harty JT, Badovinac VP (2011) Secondary CD8+ T-cell responses are controlled by systemic inflammation. Eur J Immunol 41: 1321–1333. doi: 10.1002/eji.201040730 21425157
30. Jabbari A, Harty JT (2006) Secondary memory CD8+ T cells are more protective but slower to acquire a central-memory phenotype. J Exp Med 203: 919–932. 16567385
31. Kalia V, Sarkar S, Subramaniam S, Haining WN, Smith KA, et al. (2010) Prolonged interleukin-2Ralpha expression on virus-specific CD8+ T cells favors terminal-effector differentiation in vivo. Immunity 32: 91–103. doi: 10.1016/j.immuni.2009.11.010 20096608
32. Pipkin ME, Sacks JA, Cruz-Guilloty F, Lichtenheld MG, Bevan MJ, et al. (2010) Interleukin-2 and inflammation induce distinct transcriptional programs that promote the differentiation of effector cytolytic T cells. Immunity 32: 79–90. doi: 10.1016/j.immuni.2009.11.012 20096607
33. Badovinac VP, Haring JS, Harty JT (2007) Initial T cell receptor transgenic cell precursor frequency dictates critical aspects of the CD8(+) T cell response to infection. Immunity 26: 827–841. 17555991
34. Haring JS, Jing X, Bollenbacher-Reilley J, Xue HH, Leonard WJ, et al. (2008) Constitutive expression of IL-7 receptor alpha does not support increased expansion or prevent contraction of antigen-specific CD4 or CD8 T cells following Listeria monocytogenes infection. J Immunol 180: 2855–2862. 18292507
35. Joshi NS, Cui W, Chandele A, Lee HK, Urso DR, et al. (2007) Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor. Immunity 27: 281–295. 17723218
36. Kaech SM, Tan JT, Wherry EJ, Konieczny BT, Surh CD, et al. (2003) Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat Immunol 4: 1191–1198. 14625547
37. Kaech SM, Cui W (2012) Transcriptional control of effector and memory CD8+ T cell differentiation. Nat Rev Immunol 12: 749–761. doi: 10.1038/nri3307 23080391
38. Rutishauser RL, Kaech SM (2010) Generating diversity: transcriptional regulation of effector and memory CD8 T-cell differentiation. Immunol Rev 235: 219–233. doi: 10.1111/j.0105-2896.2010.00901.x 20536566
39. Intlekofer AM, Takemoto N, Wherry EJ, Longworth SA, Northrup JT, et al. (2005) Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin. Nat Immunol 6: 1236–1244. 16273099
40. Wherry EJ, Teichgraber V, Becker TC, Masopust D, Kaech SM, et al. (2003) Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat Immunol 4: 225–234. 12563257
41. Zhou X, Xue HH (2012) Cutting edge: generation of memory precursors and functional memory CD8+ T cells depends on T cell factor-1 and lymphoid enhancer-binding factor-1. J Immunol 189: 2722–2726. doi: 10.4049/jimmunol.1201150 22875805
42. Zhou X, Yu S, Zhao DM, Harty JT, Badovinac VP, et al. (2010) Differentiation and persistence of memory CD8(+) T cells depend on T cell factor 1. Immunity 33: 229–240. doi: 10.1016/j.immuni.2010.08.002 20727791
43. Rutishauser RL, Martins GA, Kalachikov S, Chandele A, Parish IA, et al. (2009) Transcriptional repressor Blimp-1 promotes CD8(+) T cell terminal differentiation and represses the acquisition of central memory T cell properties. Immunity 31: 296–308. doi: 10.1016/j.immuni.2009.05.014 19664941
44. Jabbari A, Legge KL, Harty JT (2006) T cell conditioning explains early disappearance of the memory CD8 T cell response to infection. J Immunol 177: 3012–3018. 16920937
45. Kaech SM, Hemby S, Kersh E, Ahmed R (2002) Molecular and functional profiling of memory CD8 T cell differentiation. Cell 111: 837–851. 12526810
46. Martin MD, Condotta SA, Harty JT, Badovinac VP (2012) Population dynamics of naive and memory CD8 T cell responses after antigen stimulations in vivo. J Immunol 188: 1255–1265. doi: 10.4049/jimmunol.1101579 22205031
47. Masopust D, Ha SJ, Vezys V, Ahmed R (2006) Stimulation history dictates memory CD8 T cell phenotype: implications for prime-boost vaccination. J Immunol 177: 831–839. 16818737
48. Starbeck-Miller GR, Xue HH, Harty JT (2014) IL-12 and type I interferon prolong the division of activated CD8 T cells by maintaining high-affinity IL-2 signaling in vivo. J Exp Med 211: 105–120. doi: 10.1084/jem.20130901 24367005
49. Boyman O, Sprent J (2012) The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol 12: 180–190. doi: 10.1038/nri3156 22343569
50. Xue HH, Kovanen PE, Pise-Masison CA, Berg M, Radovich MF, et al. (2002) IL-2 negatively regulates IL-7 receptor alpha chain expression in activated T lymphocytes. Proc Natl Acad Sci U S A 99: 13759–13764. 12354940
51. Boyman O, Kovar M, Rubinstein MP, Surh CD, Sprent J (2006) Selective stimulation of T cell subsets with antibody-cytokine immune complexes. Science 311: 1924–1927. 16484453
52. Bousso P, Levraud JP, Kourilsky P, Abastado JP (1999) The composition of a primary T cell response is largely determined by the timing of recruitment of individual T cell clones. J Exp Med 189: 1591–1600. 10330438
53. van Faassen H, Saldanha M, Gilbertson D, Dudani R, Krishnan L, et al. (2005) Reducing the stimulation of CD8+ T cells during infection with intracellular bacteria promotes differentiation primarily into a central (CD62LhighCD44high) subset. J Immunol 174: 5341–5350. 15843531
54. Sarkar S, Teichgraber V, Kalia V, Polley A, Masopust D, et al. (2007) Strength of stimulus and clonal competition impact the rate of memory CD8 T cell differentiation. J Immunol 179: 6704–6714. 17982060
55. Mitchell DM, Ravkov EV, Williams MA (2010) Distinct roles for IL-2 and IL-15 in the differentiation and survival of CD8+ effector and memory T cells. J Immunol 184: 6719–6730. doi: 10.4049/jimmunol.0904089 20483725
56. Obar JJ, Lefrancois L (2010) Early signals during CD8 T cell priming regulate the generation of central memory cells. J Immunol 185: 263–272. doi: 10.4049/jimmunol.1000492 20519649
57. Williams MA, Tyznik AJ, Bevan MJ (2006) Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cells. Nature 441: 890–893. 16778891
58. Obar JJ, Molloy MJ, Jellison ER, Stoklasek TA, Zhang W, et al. (2010) CD4+ T cell regulation of CD25 expression controls development of short-lived effector CD8+ T cells in primary and secondary responses. Proc Natl Acad Sci U S A 107: 193–198. doi: 10.1073/pnas.0909945107 19966302
59. Brundage RA, Smith GA, Camilli A, Theriot JA, Portnoy DA (1993) Expression and phosphorylation of the Listeria monocytogenes ActA protein in mammalian cells. Proc Natl Acad Sci U S A 90: 11890–11894. 8265643
60. Pope C, Kim SK, Marzo A, Masopust D, Williams K, et al. (2001) Organ-specific regulation of the CD8 T cell response to Listeria monocytogenes infection. J Immunol 166: 3402–3409. 11207297
61. Masopust D, Murali-Krishna K, Ahmed R (2007) Quantitating the magnitude of the lymphocytic choriomeningitis virus-specific CD8 T-cell response: it is even bigger than we thought. J Virol 81: 2002–2011. 17151096
62. Yu S, Zhou X, Steinke FC, Liu C, Chen SC, et al. (2012) The TCF-1 and LEF-1 transcription factors have cooperative and opposing roles in T cell development and malignancy. Immunity 37: 813–826. doi: 10.1016/j.immuni.2012.08.009 23103132
63. Richer MJ, Nolz JC, Harty JT (2013) Pathogen-specific inflammatory milieux tune the antigen sensitivity of CD8(+) T cells by enhancing T cell receptor signaling. Immunity 38: 140–152. doi: 10.1016/j.immuni.2012.09.017 23260194
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2015 Číslo 10
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
Najčítanejšie v tomto čísle
- Chronobiomics: The Biological Clock as a New Principle in Host–Microbial Interactions
- Interferon-γ: The Jekyll and Hyde of Malaria
- Crosslinking of a Peritrophic Matrix Protein Protects Gut Epithelia from Bacterial Exotoxins
- Modulation of the Surface Proteome through Multiple Ubiquitylation Pathways in African Trypanosomes