Immun Ageing. 2014 May 13;11:9. doi: 10.1186/1742-4933-11-9. eCollection 2014.

Impact of ageing on the response and repertoire of influenza virus-specific CD4 T cells.

Immunity & ageing : I & A

Kathleen G Lanzer, Lawrence L Johnson, David L Woodland, Marcia A Blackman

PMID: 24999367 PMCID: PMC4082670 DOI: 10.1186/1742-4933-11-9

Abstract

BACKGROUND: Ageing has been shown to reduce CD8 T cell repertoire diversity and immune responses against influenza virus infection in mice. In contrast, less is known about the impact of ageing on CD4 T cell repertoire diversity and immune response to influenza virus infection.

RESULTS: The CD4 T cell response was followed after infection of young and aged C57BL/6 mice with influenza virus using a tetramer specific for an immunodominant MHC class II epitope of the influenza virus nucleoprotein. The appearance of virus-specific CD4 T cells in the lung airways of aged mice was delayed compared to young mice, but the overall peak number and cytokine secretion profile of responding CD4 T cells was not greatly perturbed. In addition, the T cell repertoire of responding cells, determined using T cell receptor Vβ analysis, failed to show the profound effect of age we previously described for CD8 T cells. The reduced impact of age on influenza-specific CD4 T cells was consistent with a reduced effect of age on the overall CD4 compared with the CD8 T cell repertoire in specific pathogen free mice. Aged mice that were thymectomized as young adults showed an enhanced loss of the epitope-specific CD4 T cell response after influenza virus infection compared with age-matched sham-thymectomized mice, suggesting that a reduced repertoire can contribute to impaired responsiveness.

CONCLUSIONS: The diversity of the CD4 T cell repertoire and response to influenza virus is not as profoundly impaired by ageing in C57BL/6 mice as previously shown for CD8 T cells. However, adult thymectomy enhanced the impact of ageing on the response. Understanding the impact of ageing on CD4 T cell responses to influenza virus infection is an important prerequisite for developing better vaccines for the elderly.

Keywords: Ageing; CD4 T cells; Cytokine; Epitope; Influenza virus; Mouse model; T cell receptor repertoire; Thymectomy

References

1. J Virol. 2005 Aug;79(16):10514-27 - PubMed
2. Vaccine. 2006 Jan 23;24(4):457-67 - PubMed
3. J Immunol. 2011 Feb 15;186(4):2056-2064 - PubMed
4. PLoS Pathog. 2012 Feb;8(2):e1002544 - PubMed
5. Clin Immunol Immunopathol. 1988 Sep;48(3):290-6 - PubMed
6. Mech Ageing Dev. 1991 Jun 28;59(3):275-89 - PubMed
7. Immunol Rev. 2005 Jun;205:285-96 - PubMed
8. J Immunol. 1987 May 15;138(10):3120-9 - PubMed
9. J Immunol. 1993 Dec 15;151(12):6657-69 - PubMed
10. J Virol. 2012 Jun;86(12):6792-803 - PubMed
11. J Exp Med. 2004 Nov 15;200(10):1347-58 - PubMed
12. Immunol Lett. 2006 Sep 15;107(1):8-14 - PubMed
13. Curr Opin Immunol. 2009 Aug;21(4):418-24 - PubMed
14. Mech Ageing Dev. 1999 May 17;108(3):183-206 - PubMed
15. Respir Res. 2009 Nov 18;10:112 - PubMed
16. Nat Med. 2012 Jan 29;18(2):274-80 - PubMed
17. J Immunol. 1997 May 1;158(9):4493-9 - PubMed
18. J Immunol. 1992 Aug 15;149(4):1319-25 - PubMed
19. J Immunol. 2004 Jul 1;173(1):673-81 - PubMed
20. Proc Natl Acad Sci U S A. 2008 Jun 24;105(25):8691-6 - PubMed
21. Aging Dis. 2011 Oct;2(5):374-81 - PubMed
22. Int Immunol. 1998 Sep;10(9):1281-8 - PubMed
23. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7624-8 - PubMed
24. J Exp Med. 2007 Jul 9;204(7):1625-36 - PubMed
25. Eur J Immunol. 1989 Jun;19(6):977-82 - PubMed
26. Exp Gerontol. 2007 May;42(5):427-31 - PubMed
27. Vaccine. 2000 Feb 25;18(16):1686-9 - PubMed
28. J Exp Med. 1994 Feb 1;179(2):609-18 - PubMed
29. J Exp Med. 2008 Mar 17;205(3):711-23 - PubMed
30. Nat Immunol. 2004 Feb;5(2):133-9 - PubMed
31. Vaccine. 2006 Jan 23;24(4):452-6 - PubMed
32. Mol Immunol. 2002 Mar;38(11):841-8 - PubMed
33. Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21432-7 - PubMed
34. Blood. 2000 May 1;95(9):2860-8 - PubMed
35. J Immunol. 2005 Jun 1;174(11):7446-52 - PubMed
36. Proc Natl Acad Sci U S A. 2006 May 30;103(22):8447-52 - PubMed
37. J Immunol. 2012 Feb 15;188(4):1933-41 - PubMed
38. J Exp Med. 1999 Oct 4;190(7):1013-24 - PubMed
39. Immunity. 2012 Feb 24;36(2):288-97 - PubMed
40. Exp Gerontol. 2007 May;42(5):400-6 - PubMed
41. J Immunol. 2007 Jun 15;178(12):7616-22 - PubMed
42. Nat Med. 2007 Jul;13(7):843-50 - PubMed
43. J Immunol. 2010 Jun 15;184(12):6739-45 - PubMed
44. J Immunol. 2009 Jan 15;182(2):784-92 - PubMed
45. Adv Immunol. 2002;80:243-84 - PubMed
46. Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19960-5 - PubMed
47. J Exp Med. 1998 Jun 1;187(11):1839-48 - PubMed
48. J Immunol. 2006 Jan 1;176(1):301-8 - PubMed
49. J Immunol. 2008 Feb 1;180(3):1499-507 - PubMed
50. Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2989-94 - PubMed
51. Mech Ageing Dev. 2002 Apr 30;123(8):1167-81 - PubMed
52. Immunology. 1983 Jun;49(2):387-92 - PubMed
53. J Immunol. 2012 Dec 1;189(11):5356-66 - PubMed
54. J Immunol. 2006 May 15;176(10):6333-9 - PubMed
55. Vaccine. 2011 Nov 3;29(47):8606-14 - PubMed
56. Immunology. 1991 Apr;72(4):514-9 - PubMed
57. Science. 1996 Jul 5;273(5271):70-4 - PubMed
58. Aging (Albany NY). 2010 Mar 20;2(2):78-81 - PubMed
59. Curr Opin Virol. 2013 Aug;3(4):425-9 - PubMed
60. Mech Ageing Dev. 1989 Mar;47(3):175-85 - PubMed

Publication Types

• Journal Article

Grant support

• P01 AG021600/AG/NIA NIH HHS/United States
• R01 AG032128/AG/NIA NIH HHS/United States
• R01 AG039485/AG/NIA NIH HHS/United States