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Walker LJ, Marrinan E, Muenchhoff M, et al. CD8αα Expression Marks Terminally Differentiated Human CD8+ T Cells Expanded in Chronic Viral Infection. Front Immunol. 2013;4:223doi: 10.3389/fimmu.2013.00223.
Walker, L. J., Marrinan, E., Muenchhoff, M., Ferguson, J., Kloverpris, H., Cheroutre, H., Barnes, E., Goulder, P., & Klenerman, P. (2013). CD8αα Expression Marks Terminally Differentiated Human CD8+ T Cells Expanded in Chronic Viral Infection. Frontiers in immunology, 4223. https://doi.org/10.3389/fimmu.2013.00223
Walker, L J, et al. "CD8αα Expression Marks Terminally Differentiated Human CD8+ T Cells Expanded in Chronic Viral Infection." Frontiers in immunology vol. 4 (2013): 223. doi: https://doi.org/10.3389/fimmu.2013.00223
Walker LJ, Marrinan E, Muenchhoff M, Ferguson J, Kloverpris H, Cheroutre H, Barnes E, Goulder P, Klenerman P. CD8αα Expression Marks Terminally Differentiated Human CD8+ T Cells Expanded in Chronic Viral Infection. Front Immunol. 2013 Aug 06;4:223. doi: 10.3389/fimmu.2013.00223. eCollection 2013. PMID: 23964274; PMCID: PMC3734367.
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Front Immunol. 2013 Aug 06;4:223. doi: 10.3389/fimmu.2013.00223. eCollection 2013.

CD8αα Expression Marks Terminally Differentiated Human CD8+ T Cells Expanded in Chronic Viral Infection.

Frontiers in immunology

L J Walker, E Marrinan, M Muenchhoff, J Ferguson, H Kloverpris, H Cheroutre, E Barnes, P Goulder, Paul Klenerman

Affiliations

  1. Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford , Oxford , UK ; Institute of Cellular Medicine, Newcastle University , Newcastle upon Tyne , UK.

PMID: 23964274 PMCID: PMC3734367 DOI: 10.3389/fimmu.2013.00223

Abstract

The T cell co-receptor CD8αβ enhances T cell sensitivity to antigen, however studies indicate CD8αα has the converse effect and acts as a co-repressor. Using a combination of Thymic Leukemia (TL) antigen tetramer, which directly binds CD8αα, anti-CD161, and anti-Vα7.2 antibodies we have been able for the first time to clearly define CD8αα expression on human CD8 T cells subsets. In healthy controls CD8αα is most highly expressed by CD161 "bright" (CD161++) mucosal associated invariant T (MAIT) cells, with CD8αα expression highly restricted to the TCR Vα7.2+ cells of this subset. We also identified CD8αα-expressing populations within the CD161 "mid" (CD161+) and "negative" (CD161-) non-MAIT CD8 T cell subsets and show TL-tetramer binding to correlate with expression of CD8β at low levels in the context of maintained CD8α expression (CD8α+CD8β(low)). In addition, we found CD161-CD8α+CD8β(low) populations to be significantly expanded in the peripheral blood of HIV-1 and hepatitis B (mean of 47 and 40% of CD161- T cells respectively) infected individuals. Such CD8αα expressing T cells are an effector-memory population (CD45RA-, CCR7-, CD62L-) that express markers of activation and maturation (HLA-DR+, CD28-, CD27-, CD57+) and are functionally distinct, expressing greater levels of TNF-α and IFN-γ on stimulation and perforin at rest than their CD8α+CD8β(high) counterparts. Antigen-specific T cells in HLA-B(∗)4201+HIV-1 infected patients are found within both the CD161-CD8α+CD8β(high) and CD161-CD8α+CD8β(low) populations. Overall we have clearly defined CD8αα expressing human T cell subsets using the TL-tetramer, and have demonstrated CD161-CD8α+CD8β(low) populations, highly expanded in disease settings, to co-express CD8αβ and CD8αα. Co-expression of CD8αα on CD8αβ T cells may impact on their overall function in vivo and contribute to the distinctive phenotype of highly differentiated populations in HBV and HIV-1 infection.

Keywords: CD8+ T cells; CD8α; HIV-1; hepatitis B; hepatitis C

References

  1. Eur J Immunol. 1991 Aug;21(8):1793-800 - PubMed
  2. Immunity. 2003 Feb;18(2):255-64 - PubMed
  3. J Immunol. 2003 Nov 1;171(9):4493-503 - PubMed
  4. Cell Immunol. 2000 Apr 10;201(1):58-62 - PubMed
  5. Tissue Antigens. 2007 Sep;70(3):179-89 - PubMed
  6. Blood. 2011 Aug 25;118(8):2138-49 - PubMed
  7. J Am Geriatr Soc. 2010 Aug;58(8):1565-75 - PubMed
  8. Eur J Immunol. 2007 Jun;37(6):1634-41 - PubMed
  9. Cell. 1988 Oct 21;55(2):301-8 - PubMed
  10. Exp Gerontol. 2007 May;42(5):432-7 - PubMed
  11. J Virol. 2000 Jul;74(13):5769-75 - PubMed
  12. Science. 2001 Nov 30;294(5548):1936-9 - PubMed
  13. J Immunol. 2002 Nov 15;169(10):5708-14 - PubMed
  14. Science. 2004 Apr 23;304(5670):590-3 - PubMed
  15. Clin Exp Immunol. 2010 Mar;159(3):245-55 - PubMed
  16. J Exp Med. 2008 Sep 1;205(9):2111-24 - PubMed
  17. Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4102-7 - PubMed
  18. J Immunol. 1992 Sep 1;149(5):1613-8 - PubMed
  19. Vaccine. 2006 Feb 20;24(8):1159-69 - PubMed
  20. J Immunol. 2005 Mar 15;174(6):3501-7 - PubMed
  21. Immunology. 2009 Feb;126(2):147-64 - PubMed
  22. Blood. 1998 Jul 1;92(1):198-206 - PubMed
  23. Blood. 2002 Dec 1;100(12):4090-7 - PubMed
  24. J Immunol. 2002 Oct 1;169(7):3492-8 - PubMed
  25. Scand J Immunol. 2008 May;67(5):501-8 - PubMed
  26. Blood. 1997 Nov 1;90(9):3662-72 - PubMed
  27. J Immunol. 2002 Apr 15;168(8):3881-6 - PubMed
  28. J Biol Chem. 2007 Aug 17;282(33):23799-810 - PubMed
  29. J Immunol. 2008 Jun 1;180(11):7276-86 - PubMed
  30. J Immunol. 2009 Jul 15;183(2):1044-54 - PubMed
  31. Aging Dis. 2011 Oct;2(5):382-397 - PubMed
  32. Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3006-11 - PubMed
  33. Clin Immunol Immunopathol. 1996 Nov;81(2):129-35 - PubMed
  34. Clin Exp Immunol. 2003 Sep;133(3):334-43 - PubMed
  35. Immunity. 2006 Oct;25(4):631-41 - PubMed
  36. J Biol Chem. 2005 Jul 29;280(30):27491-501 - PubMed
  37. Nat Med. 2002 Apr;8(4):379-85 - PubMed
  38. Nat Immunol. 2011 Oct 02;12(11):1086-95 - PubMed
  39. Immun Ageing. 2007 Dec 11;4:9 - PubMed
  40. Blood. 2012 Jan 12;119(2):422-33 - PubMed
  41. J Immunol. 2011 Feb 15;186(4):2672-80 - PubMed
  42. J Exp Med. 1996 Dec 1;184(6):2439-44 - PubMed
  43. Semin Immunol. 2012 Oct;24(5):373-82 - PubMed
  44. Immunity. 2003 Feb;18(2):205-15 - PubMed
  45. Immunity. 2008 Feb;28(2):149-59 - PubMed
  46. PLoS Biol. 2004 Feb;2(2):E20 - PubMed

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