IL-15 as a mediator of CD4+ help for CD8+ T cell longevity and avoidance of TRAIL-mediated apoptosis

SangKon Oh, Liyanage P. Perera, Masaki Terabe, Ling Ni, Thomas A. Waldmann, Jay A. Berzofsky

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

CD4+ helper T cells contribute to the induction and maintenance of antigen-specific CD8+ T cells. Their absence results in short-lived antigen-specific CD8+ T cells and defective secondary CD8+ T cell responses because of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Here, we show that IL-15 codelivered with vaccines can overcome CD4+ T cell deficiency for promoting longevity of antigen-specific CD8+ T cells and avoidance of TRAIL-mediated apoptosis. In both priming and secondary responses, IL-15 down-regulates proapoptotic Bax, an intermediate in TRAIL-mediated apoptosis, and increases anti-apoptotic Bcl-XL in CD8+ T cells. Thus, IL-15 is sufficient to mimic CD4+ T cell help. Antigen-specific CD4+ T cells induce dendritic cells (DCs) to produce IL-15. IL-15 is also necessary for optimal help, because helper cells do not deliver effective help through IL-15-/- DCs. Therefore, IL-15 codelivered with vaccines can overcome CD4+ helper T cell deficiency for induction of functionally efficient CD8+ T cells and maintenance of CD8 + cytotoxic T lymphocytes (CTLs), and IL-15 is probably one of the natural mediators of help. These findings suggest new vaccine strategies against infections and cancers, especially in individuals with CD4-deficiency.

Original languageEnglish (US)
Pages (from-to)5201-5206
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number13
DOIs
StatePublished - Apr 1 2008
Externally publishedYes

Fingerprint

Interleukin-15
Apoptosis
T-Lymphocytes
CD8 Antigens
Helper-Inducer T-Lymphocytes
Vaccines
Dendritic Cells
Maintenance
CD4 Antigens
Cytotoxic T-Lymphocytes
Down-Regulation
Tumor Necrosis Factor-alpha
Ligands

Keywords

  • Cytotoxic T lymphocytes
  • T cell help

ASJC Scopus subject areas

  • General

Cite this

IL-15 as a mediator of CD4+ help for CD8+ T cell longevity and avoidance of TRAIL-mediated apoptosis. / Oh, SangKon; Perera, Liyanage P.; Terabe, Masaki; Ni, Ling; Waldmann, Thomas A.; Berzofsky, Jay A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 13, 01.04.2008, p. 5201-5206.

Research output: Contribution to journalArticle

Oh, SangKon ; Perera, Liyanage P. ; Terabe, Masaki ; Ni, Ling ; Waldmann, Thomas A. ; Berzofsky, Jay A. / IL-15 as a mediator of CD4+ help for CD8+ T cell longevity and avoidance of TRAIL-mediated apoptosis. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 13. pp. 5201-5206.
@article{b758b5f054ff4e66ad523cea59a762c8,
title = "IL-15 as a mediator of CD4+ help for CD8+ T cell longevity and avoidance of TRAIL-mediated apoptosis",
abstract = "CD4+ helper T cells contribute to the induction and maintenance of antigen-specific CD8+ T cells. Their absence results in short-lived antigen-specific CD8+ T cells and defective secondary CD8+ T cell responses because of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Here, we show that IL-15 codelivered with vaccines can overcome CD4+ T cell deficiency for promoting longevity of antigen-specific CD8+ T cells and avoidance of TRAIL-mediated apoptosis. In both priming and secondary responses, IL-15 down-regulates proapoptotic Bax, an intermediate in TRAIL-mediated apoptosis, and increases anti-apoptotic Bcl-XL in CD8+ T cells. Thus, IL-15 is sufficient to mimic CD4+ T cell help. Antigen-specific CD4+ T cells induce dendritic cells (DCs) to produce IL-15. IL-15 is also necessary for optimal help, because helper cells do not deliver effective help through IL-15-/- DCs. Therefore, IL-15 codelivered with vaccines can overcome CD4+ helper T cell deficiency for induction of functionally efficient CD8+ T cells and maintenance of CD8 + cytotoxic T lymphocytes (CTLs), and IL-15 is probably one of the natural mediators of help. These findings suggest new vaccine strategies against infections and cancers, especially in individuals with CD4-deficiency.",
keywords = "Cytotoxic T lymphocytes, T cell help",
author = "SangKon Oh and Perera, {Liyanage P.} and Masaki Terabe and Ling Ni and Waldmann, {Thomas A.} and Berzofsky, {Jay A.}",
year = "2008",
month = "4",
day = "1",
doi = "10.1073/pnas.0801003105",
language = "English (US)",
volume = "105",
pages = "5201--5206",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "13",

}

TY - JOUR

T1 - IL-15 as a mediator of CD4+ help for CD8+ T cell longevity and avoidance of TRAIL-mediated apoptosis

AU - Oh, SangKon

AU - Perera, Liyanage P.

AU - Terabe, Masaki

AU - Ni, Ling

AU - Waldmann, Thomas A.

AU - Berzofsky, Jay A.

PY - 2008/4/1

Y1 - 2008/4/1

N2 - CD4+ helper T cells contribute to the induction and maintenance of antigen-specific CD8+ T cells. Their absence results in short-lived antigen-specific CD8+ T cells and defective secondary CD8+ T cell responses because of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Here, we show that IL-15 codelivered with vaccines can overcome CD4+ T cell deficiency for promoting longevity of antigen-specific CD8+ T cells and avoidance of TRAIL-mediated apoptosis. In both priming and secondary responses, IL-15 down-regulates proapoptotic Bax, an intermediate in TRAIL-mediated apoptosis, and increases anti-apoptotic Bcl-XL in CD8+ T cells. Thus, IL-15 is sufficient to mimic CD4+ T cell help. Antigen-specific CD4+ T cells induce dendritic cells (DCs) to produce IL-15. IL-15 is also necessary for optimal help, because helper cells do not deliver effective help through IL-15-/- DCs. Therefore, IL-15 codelivered with vaccines can overcome CD4+ helper T cell deficiency for induction of functionally efficient CD8+ T cells and maintenance of CD8 + cytotoxic T lymphocytes (CTLs), and IL-15 is probably one of the natural mediators of help. These findings suggest new vaccine strategies against infections and cancers, especially in individuals with CD4-deficiency.

AB - CD4+ helper T cells contribute to the induction and maintenance of antigen-specific CD8+ T cells. Their absence results in short-lived antigen-specific CD8+ T cells and defective secondary CD8+ T cell responses because of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Here, we show that IL-15 codelivered with vaccines can overcome CD4+ T cell deficiency for promoting longevity of antigen-specific CD8+ T cells and avoidance of TRAIL-mediated apoptosis. In both priming and secondary responses, IL-15 down-regulates proapoptotic Bax, an intermediate in TRAIL-mediated apoptosis, and increases anti-apoptotic Bcl-XL in CD8+ T cells. Thus, IL-15 is sufficient to mimic CD4+ T cell help. Antigen-specific CD4+ T cells induce dendritic cells (DCs) to produce IL-15. IL-15 is also necessary for optimal help, because helper cells do not deliver effective help through IL-15-/- DCs. Therefore, IL-15 codelivered with vaccines can overcome CD4+ helper T cell deficiency for induction of functionally efficient CD8+ T cells and maintenance of CD8 + cytotoxic T lymphocytes (CTLs), and IL-15 is probably one of the natural mediators of help. These findings suggest new vaccine strategies against infections and cancers, especially in individuals with CD4-deficiency.

KW - Cytotoxic T lymphocytes

KW - T cell help

UR - http://www.scopus.com/inward/record.url?scp=42449106871&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42449106871&partnerID=8YFLogxK

U2 - 10.1073/pnas.0801003105

DO - 10.1073/pnas.0801003105

M3 - Article

C2 - 18362335

AN - SCOPUS:42449106871

VL - 105

SP - 5201

EP - 5206

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 13

ER -