Home LiteratureArticle Details
PMID: 21804558 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Autocrine IL-2 is required for secondary population expansion of CD8(+) memory T cells.

Nature immunology ·Vol. 12 ·No. 9 ·2011-07-31 ·Pages 908-13

Feau S, Arens R, Togher S, Schoenberger SP

Abstract

Two competing theories have been put forward to explain the role of CD4(+) T cells in priming CD8(+) memory T cells: one proposes paracrine secretion of interleukin 2 (IL-2); the other proposes the activation of antigen-presenting cells (APCs) via the costimulatory molecule CD40 and its ligand CD40L. We investigated the requirement for IL-2 by the relevant three cell types in vivo and found that CD8(+) T cells, rather than CD4(+) T cells or dendritic cells (DCs), produced the IL-2 necessary for CD8(+) T cell memory. Il2(-/-) CD4(+) T cells were able to provide help only if their ability to transmit signals via CD40L was intact. Our findings reconcile contradictory elements implicit in each model noted above by showing that CD4(+) T cells activate APCs through a CD40L-dependent mechanism to enable autocrine production of IL-2 in CD8(+) memory T cells.

MeSH Terms
Animals Autocrine Communication CD4-Positive T-Lymphocytes/cytology,immunology,metabolism CD40 Antigens/immunology,metabolism CD40 Ligand/immunology,metabolism CD8-Positive T-Lymphocytes/cytology,immunology,metabolism Cell Proliferation Dendritic Cells/cytology,immunology,metabolism Flow Cytometry Immunologic Memory Interleukin-2/immunology,metabolism Listeria monocytogenes/growth & development Listeriosis/immunology,microbiology Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Knockout Signal Transduction/immunology
Chemicals
CD40 Antigens Interleukin-2 CD40 Ligand
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Feau Sonia
Laboratory of Cellular Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
Arens Ramon
Togher Susan
Schoenberger Stephen P
References (40)
40 references, click to expand
  1. Immunological memory and protective immunity: understanding their relation.
    Science. 1996 Apr 5;272(5258):54-60 PMID: 8600537
  2. Help for cytotoxic-T-cell responses is mediated by CD40 signalling.
    Nature. 1998 Jun 4;393(6684):478-80 PMID: 9624004
  3. Immune responses in interleukin-2-deficient mice.
    Science. 1993 Nov 12;262(5136):1059-61 PMID: 8235625
  4. A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell.
    Nature. 1998 Jun 4;393(6684):474-8 PMID: 9624003
  5. Interleukin-2 deficient mice: a new model to study autoimmunity and self-tolerance.
    Immunol Rev. 1995 Dec;148:35-44 PMID: 8825281
  6. Development and function of T cells in mice rendered interleukin-2 deficient by gene targeting.
    Nature. 1991 Aug 15;352(6336):621-4 PMID: 1830926
  7. CD4+ T cell help impairs CD8+ T cell deletion induced by cross-presentation of self-antigens and favors autoimmunity.
    J Exp Med. 1997 Dec 15;186(12):2057-62 PMID: 9396776
  8. Protein kinase B controls transcriptional programs that direct cytotoxic T cell fate but is dispensable for T cell metabolism.
    Immunity. 2011 Feb 25;34(2):224-36 PMID: 21295499
  9. A contribution of mouse dendritic cell-derived IL-2 for NK cell activation.
    J Exp Med. 2004 Aug 2;200(3):287-95 PMID: 15289500
  10. Requirement for CD4 T cell help in generating functional CD8 T cell memory.
    Science. 2003 Apr 11;300(5617):337-9 PMID: 12690201
  11. Three-cell-type clusters of T cells with antigen-presenting cells best explain the epitope linkage and noncognate requirements of the in vivo cytolytic response.
    Eur J Immunol. 1987 Nov;17(11):1579-83 PMID: 2445585
  12. Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cells.
    Nature. 2006 Jun 15;441(7095):890-3 PMID: 16778891
  13. A role for CD40 expression on CD8+ T cells in the generation of CD8+ T cell memory.
    Science. 2002 Sep 20;297(5589):2060-3 PMID: 12242444
  14. The role of programming in memory T-cell development.
    Curr Opin Immunol. 2004 Apr;16(2):217-25 PMID: 15023416
  15. Chemokines enhance immunity by guiding naive CD8+ T cells to sites of CD4+ T cell-dendritic cell interaction.
    Nature. 2006 Apr 13;440(7086):890-5 PMID: 16612374
  16. Differences in dendritic cells stimulated in vivo by tumors engineered to secrete granulocyte-macrophage colony-stimulating factor or Flt3-ligand.
    Cancer Res. 2000 Jun 15;60(12):3239-46 PMID: 10866317
  17. Tolerance, not immunity, crucially depends on IL-2.
    Nat Rev Immunol. 2004 Sep;4(9):665-74 PMID: 15343366
  18. IL-2 is not required for the initiation of CD8 T cell cycling but sustains expansion.
    J Immunol. 2003 Dec 1;171(11):5727-35 PMID: 14634080
  19. Interleukin-2 and inflammation induce distinct transcriptional programs that promote the differentiation of effector cytolytic T cells.
    Immunity. 2010 Jan 29;32(1):79-90 PMID: 20096607
  20. Characterization of the ovalbumin-specific TCR transgenic line OT-I: MHC elements for positive and negative selection.
    Immunol Cell Biol. 2000 Apr;78(2):110-7 PMID: 10762410
  21. Initial T cell receptor transgenic cell precursor frequency dictates critical aspects of the CD8(+) T cell response to infection.
    Immunity. 2007 Jun;26(6):827-41 PMID: 17555991
  22. Defective CD8 T cell memory following acute infection without CD4 T cell help.
    Science. 2003 Apr 11;300(5617):339-42 PMID: 12690202
  23. Early IL-2 production by mouse dendritic cells is the result of microbial-induced priming.
    J Immunol. 2003 May 15;170(10):5075-81 PMID: 12734352
  24. Constitutive class I-restricted exogenous presentation of self antigens in vivo.
    J Exp Med. 1996 Sep 1;184(3):923-30 PMID: 9064352
  25. CD4+ T-cell help controls CD8+ T-cell memory via TRAIL-mediated activation-induced cell death.
    Nature. 2005 Mar 3;434(7029):88-93 PMID: 15744305
  26. Role of self-peptides in positively selecting the T-cell repertoire.
    Nature. 1990 Mar 1;344(6261):65-7 PMID: 2304556
  27. Naïve CTLs require a single brief period of antigenic stimulation for clonal expansion and differentiation.
    Nat Immunol. 2001 May;2(5):423-9 PMID: 11323696
  28. CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes.
    Nature. 2003 Feb 20;421(6925):852-6 PMID: 12594515
  29. Cutting edge: CD4+ T cell-derived IL-2 is essential for help-dependent primary CD8+ T cell responses.
    J Immunol. 2008 Dec 1;181(11):7445-8 PMID: 19017930
  30. Immunology. Licence to kill.
    Nature. 1998 Jun 4;393(6684):413-4 PMID: 9623994
  31. Prolonged interleukin-2Ralpha expression on virus-specific CD8+ T cells favors terminal-effector differentiation in vivo.
    Immunity. 2010 Jan 29;32(1):91-103 PMID: 20096608
  32. Helper activity is required for the in vivo generation of cytotoxic T lymphocytes.
    J Exp Med. 1982 Mar 1;155(3):768-82 PMID: 6801178
  33. Development of a novel transgenic mouse for the study of interactions between CD4 and CD8 T cells during graft rejection.
    Am J Transplant. 2003 Nov;3(11):1355-62 PMID: 14525595
  34. T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions.
    Nature. 1998 Jun 4;393(6684):480-3 PMID: 9624005
  35. Dynamic programming of CD8+ T lymphocyte responses.
    Nat Immunol. 2003 Apr;4(4):361-5 PMID: 12640451
  36. Generalized autoimmune disease in interleukin-2-deficient mice is triggered by an uncontrolled activation and proliferation of CD4+ T cells.
    Eur J Immunol. 1995 Nov;25(11):3053-9 PMID: 7489743
  37. The dendritic cell populations of mouse lymph nodes.
    J Immunol. 2001 Jul 15;167(2):741-8 PMID: 11441078
  38. Programmed contraction of CD8(+) T cells after infection.
    Nat Immunol. 2002 Jul;3(7):619-26 PMID: 12055624
  39. TRAIL deficiency delays, but does not prevent, erosion in the quality of "helpless" memory CD8 T cells.
    J Immunol. 2006 Jul 15;177(2):999-1006 PMID: 16818756
  40. Memory CD8+ T cell differentiation: initial antigen encounter triggers a developmental program in naïve cells.
    Nat Immunol. 2001 May;2(5):415-22 PMID: 11323695
Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.2079
Published
2011-07-31
Epub
2011-00-31
Pages
908-13
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC3388550
Subset
IM
Grants
NIAID NIH HHS · R01 AI076972 · United States
NCI NIH HHS · R01 CA081261 · United States
NCI NIH HHS · R01CA81261 · United States
External Links
PubMed source DOI: 10.1038/ni.2079 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2