Quantitative and Qualitative Deficits in Neonatal Lung-Migratory Dendritic Cells Impact the Generation of the CD8+ T Cell Response

English version České info

CD103+ and CD11b+ populations of CD11c+MHCIIhi murine dendritic cells (DCs) have been shown to carry antigens from the lung through the afferent lymphatics to mediastinal lymph nodes (MLN). We compared the responses of these two DC populations in neonatal and adult mice following intranasal infection with respiratory syncytial virus. The response in neonates was dominated by functionally-limited CD103+ DCs, while CD11b+ DCs were diminished in both number and function compared to adults. Infecting mice at intervals through the first three weeks of life revealed an evolution in DC phenotype and function during early life. Using TCR transgenic T cells with two different specificities to measure the ability of CD103+ DC to induce epitope-specific CD8+ T cell responses, we found that neonatal CD103+ DCs stimulate proliferation in a pattern distinct from adult CD103+ DCs. Blocking CD28-mediated costimulatory signals during adult infection demonstrated that signals from this costimulatory pathway influence the hierarchy of the CD8+ T cell response to RSV, suggesting that limited costimulation provided by neonatal CD103+ DCs is one mechanism whereby neonates generate a distinct CD8+ T cell response from that of adults.

Vyšlo v časopise: Quantitative and Qualitative Deficits in Neonatal Lung-Migratory Dendritic Cells Impact the Generation of the CD8+ T Cell Response. PLoS Pathog 10(2): e32767. doi:10.1371/journal.ppat.1003934
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003934

Souhrn

Zdroje

1. CondonTV, SawyerRT, FentonMJ, RichesDW (2011) Lung dendritic cells at the innate-adaptive immune interface. J Leukoc Biol 90 : 883–895.

2. DeschAN, HensonPM, JakubzickCV (2013) Pulmonary dendritic cell development and antigen acquisition. Immunol Res 55 : 178–186.

3. LambrechtBN, HammadH (2012) Lung dendritic cells in respiratory viral infection and asthma: from protection to immunopathology. Annu Rev Immunol 30 : 243–270.

4. GinhouxF, LiuK, HelftJ, BogunovicM, GreterM, et al. (2009) The origin and development of nonlymphoid tissue CD103+ DCs. J Exp Med 206 : 3115–3130.

5. del RioML, Rodriguez-BarbosaJI, KremmerE, ForsterR (2007) CD103 -⁠ and CD103+ bronchial lymph node dendritic cells are specialized in presenting and cross-presenting innocuous antigen to CD4+ and CD8+ T cells. J Immunol 178 : 6861–6866.

6. BeauchampNM, BusickRY, Alexander-MillerMA (2010) Functional divergence among CD103+ dendritic cell subpopulations following pulmonary poxvirus infection. J Virol 84 : 10191–10199.

7. GeurtsvanKesselCH, WillartMA, van RijtLS, MuskensF, KoolM, et al. (2008) Clearance of influenza virus from the lung depends on migratory langerin+CD11b -⁠ but not plasmacytoid dendritic cells. J Exp Med 205 : 1621–1634.

8. HoAW, PrabhuN, BettsRJ, GeMQ, DaiX, et al. (2011) Lung CD103+ dendritic cells efficiently transport influenza virus to the lymph node and load viral antigen onto MHC class I for presentation to CD8 T cells. J Immunol 187 : 6011–6021.

9. KimTS, BracialeTJ (2009) Respiratory dendritic cell subsets differ in their capacity to support the induction of virus-specific cytotoxic CD8+ T cell responses. PLoS One 4: e4204.

10. MoltedoB, LiW, YountJS, MoranTM (2011) Unique type I interferon responses determine the functional fate of migratory lung dendritic cells during influenza virus infection. PLoS Pathog 7: e1002345.

11. Suarez-RamirezJE, WuT, LeeYT, AguilaCC, BouchardKR, et al. (2011) Division of labor between subsets of lymph node dendritic cells determines the specificity of the CD8(+) T-cell recall response to influenza infection. Eur J Immunol 41 : 2632–2641.

12. EdelsonBT, KcW, JuangR, KohyamaM, BenoitLA, et al. (2010) Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8alpha+ conventional dendritic cells. J Exp Med 207 : 823–836.

13. HildnerK, EdelsonBT, PurthaWE, DiamondM, MatsushitaH, et al. (2008) Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Science 322 : 1097–1100.

14. DeschAN, RandolphGJ, MurphyK, GautierEL, KedlRM, et al. (2011) CD103+ pulmonary dendritic cells preferentially acquire and present apoptotic cell-associated antigen. J Exp Med 208 : 1789–1797.

15. FuruhashiK, SudaT, HasegawaH, SuzukiY, HashimotoD, et al. (2012) Mouse lung CD103+ and CD11bhigh dendritic cells preferentially induce distinct CD4+ T-cell responses. Am J Respir Cell Mol Biol 46 : 165–172.

16. KhareA, KrishnamoorthyN, OrissTB, FeiM, RayP, et al. (2013) Cutting Edge: Inhaled Antigen Upregulates Retinaldehyde Dehydrogenase in Lung CD103+ but Not Plasmacytoid Dendritic Cells To Induce Foxp3 De Novo in CD4+ T cells and Promote Airway Tolerance. J Immunol. 191 : 25–9.

17. BeatySR, RoseCEJr, SungSS (2007) Diverse and potent chemokine production by lung CD11bhigh dendritic cells in homeostasis and in allergic lung inflammation. J Immunol 178 : 1882–1895.

18. MesnilC, SabatelCM, MarichalT, ToussaintM, CataldoD, et al. (2012) Resident CD11b(+)Ly6C(-) lung dendritic cells are responsible for allergic airway sensitization to house dust mite in mice. PLoS One 7: e53242.

19. PlantingaM, GuilliamsM, VanheerswynghelsM, DeswarteK, Branco-MadeiraF, et al. (2013) Conventional and monocyte-derived CD11b(+) dendritic cells initiate and maintain T helper 2 cell-mediated immunity to house dust mite allergen. Immunity 38 : 322–335.

20. LozanoR, NaghaviM, ForemanK, LimS, ShibuyaK, et al. (2012) Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380 : 2095–2128.

21. LukensMV, KruijsenD, CoenjaertsFE, KimpenJL, van BleekGM (2009) Respiratory syncytial virus-induced activation and migration of respiratory dendritic cells and subsequent antigen presentation in the lung-draining lymph node. J Virol 83 : 7235–7243.

22. RuckwardtTJ, MalloyAM, GostickE, PriceDA, DashP, et al. (2011) Neonatal CD8 T-cell hierarchy is distinct from adults and is influenced by intrinsic T cell properties in respiratory syncytial virus infected mice. PLoS Pathog 7: e1002377.

23. TregoningJS, YamaguchiY, HarkerJ, WangB, OpenshawPJ (2008) The role of T cells in the enhancement of respiratory syncytial virus infection severity during adult reinfection of neonatally sensitized mice. J Virol 82 : 4115–4124.

24. TuostoL, AcutoO (1998) CD28 affects the earliest signaling events generated by TCR engagement. Eur J Immunol 28 : 2131–2142.

25. WulfingC, SumenC, SjaastadMD, WuLC, DustinML, et al. (2002) Costimulation and endogenous MHC ligands contribute to T cell recognition. Nat Immunol 3 : 42–47.

26. RihaP, RuddCE (2010) CD28 co-signaling in the adaptive immune response. Self Nonself 1 : 231–240.

27. SeahSG, CarringtonEM, NgWC, BelzGT, BradyJL, et al. (2012) Unlike CD4+ T-cell help, CD28 costimulation is necessary for effective primary CD8+ T-cell influenza-specific immunity. Eur J Immunol 42 : 1744–1754.

28. BouguermouhS, FortinG, BabaN, RubioM, SarfatiM (2009) CD28 co-stimulation down regulates Th17 development. PLoS One 4: e5087.

29. SempleK, NguyenA, YuY, WangH, AnasettiC, et al. (2011) Strong CD28 costimulation suppresses induction of regulatory T cells from naive precursors through Lck signaling. Blood 117 : 3096–3103.

30. Ballesteros-TatoA, LeonB, LundFE, RandallTD (2010) Temporal changes in dendritic cell subsets, cross-priming and costimulation via CD70 control CD8(+) T cell responses to influenza. Nat Immunol 11 : 216–224.

31. van GisbergenKP, KlarenbeekPL, KragtenNA, UngerPP, NieuwenhuisMB, et al. (2011) The costimulatory molecule CD27 maintains clonally diverse CD8(+) T cell responses of low antigen affinity to protect against viral variants. Immunity 35 : 97–108.

32. BachmannMF, SebzdaE, KundigTM, ShahinianA, SpeiserDE, et al. (1996) T cell responses are governed by avidity and co-stimulatory thresholds. Eur J Immunol 26 : 2017–2022.

33. ChenW, BenninkJR, MortonPA, YewdellJW (2002) Mice deficient in perforin, CD4+ T cells, or CD28-mediated signaling maintain the typical immunodominance hierarchies of CD8+ T-cell responses to influenza virus. J Virol 76 : 10332–10337.

34. HeidemaJ, LukensMV, van MarenWW, van DijkME, OttenHG, et al. (2007) CD8+ T cell responses in bronchoalveolar lavage fluid and peripheral blood mononuclear cells of infants with severe primary respiratory syncytial virus infections. J Immunol 179 : 8410–8417.

35. LukensMV, van de PolAC, CoenjaertsFE, JansenNJ, KampVM, et al. (2010) A systemic neutrophil response precedes robust CD8(+) T-cell activation during natural respiratory syncytial virus infection in infants. J Virol 84 : 2374–2383.

36. BillamP, BonaparteKL, LiuJ, RuckwardtTJ, ChenM, et al. (2011) T Cell receptor clonotype influences epitope hierarchy in the CD8+ T cell response to respiratory syncytial virus infection. J Biol Chem 286 : 4829–4841.

37. CandonS, McHughRS, FoucrasG, NatarajanK, ShevachEM, et al. (2004) Spontaneous organ-specific Th2-mediated autoimmunity in TCR transgenic mice. J Immunol 172 : 2917–2924.

38. HallakLK, SpillmannD, CollinsPL, PeeplesME (2000) Glycosaminoglycan sulfation requirements for respiratory syncytial virus infection. J Virol 74 : 10508–10513.