Evaluation of OX40 ligand as a costimulator of human antiviral memory CD8 T cell responses: Comparison with B7.1 and 4-1BBL

Lena Serghides, Jacob Bukczynski, Tao Wen, Chao Wang, Jean Pierre Routy, Mohamed Rachid Boulassel, Rafick Pierre Sekaly, Mario Ostrowski, Nicole F. Bernard, Tania H. Watts

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

CTL are important effectors of antiviral immunity. Designing adjuvants that can induce strong cytotoxic T cell responses in humans would greatly improve the effectiveness of an antiviral vaccination or therapeutic strategy. Recent evidence suggests that, in addition to its well-established role in costimulation of CD4 T cell responses, OX40L (CD134) can directly costimulate mouse CD8 T cells. In this study, we evaluated the role of OX40L in costimulation of human antiviral CD8 T cell responses and compared it with two other important costimulators, B7.1 (CD80) and 4-1BBL (CD137L). Delivery of OX40L to human monocytes using a recombinant replication-defective adenovirus led to greater expansion, up-regulation of perforin, enhanced cytolytic activity, and increased numbers of IFN-γ-and TNF-α-producing antiviral memory CD8 T cells in cultures of total T eels. Synergistic or additive effects were observed when OX40L costimulation was combined with 4-1BBL (CD137L) or B7.1 (CD80) costimulation. In total T cell cultures, at low Ag dose, 4-1BBL provided the most potent costimulus for influenza-specific CD8 T cell expansion, followed by B7.1 (CD80) and then OX40L. For isolated CD8 T cells, 4-1BBL was also the most consistent costimulator, followed by B7.1. In contrast, OX40L showed efficacy in direct activation of memory CD8 T cells in only one of seven donors. Thus, OX40L costimulates human antiviral memory CD8 T cell responses largely through indirect effects and can enhance anti-influenza, anti-EBV, and anti-HIV responses, particularly in combination with 4-1BBL or B7.

Original languageEnglish
Pages (from-to)6368-6377
Number of pages10
JournalJournal of Immunology
Volume175
Issue number10
Publication statusPublished - Nov 15 2005

Fingerprint

OX40 Ligand
Antiviral Agents
T-Lymphocytes
Human Influenza
Cell Culture Techniques
Eels
Perforin
Human Herpesvirus 4
Adenoviridae
Monocytes
Immunity

ASJC Scopus subject areas

  • Immunology

Cite this

Serghides, L., Bukczynski, J., Wen, T., Wang, C., Routy, J. P., Boulassel, M. R., ... Watts, T. H. (2005). Evaluation of OX40 ligand as a costimulator of human antiviral memory CD8 T cell responses: Comparison with B7.1 and 4-1BBL. Journal of Immunology, 175(10), 6368-6377.

Evaluation of OX40 ligand as a costimulator of human antiviral memory CD8 T cell responses : Comparison with B7.1 and 4-1BBL. / Serghides, Lena; Bukczynski, Jacob; Wen, Tao; Wang, Chao; Routy, Jean Pierre; Boulassel, Mohamed Rachid; Sekaly, Rafick Pierre; Ostrowski, Mario; Bernard, Nicole F.; Watts, Tania H.

In: Journal of Immunology, Vol. 175, No. 10, 15.11.2005, p. 6368-6377.

Research output: Contribution to journalArticle

Serghides, L, Bukczynski, J, Wen, T, Wang, C, Routy, JP, Boulassel, MR, Sekaly, RP, Ostrowski, M, Bernard, NF & Watts, TH 2005, 'Evaluation of OX40 ligand as a costimulator of human antiviral memory CD8 T cell responses: Comparison with B7.1 and 4-1BBL', Journal of Immunology, vol. 175, no. 10, pp. 6368-6377.
Serghides, Lena ; Bukczynski, Jacob ; Wen, Tao ; Wang, Chao ; Routy, Jean Pierre ; Boulassel, Mohamed Rachid ; Sekaly, Rafick Pierre ; Ostrowski, Mario ; Bernard, Nicole F. ; Watts, Tania H. / Evaluation of OX40 ligand as a costimulator of human antiviral memory CD8 T cell responses : Comparison with B7.1 and 4-1BBL. In: Journal of Immunology. 2005 ; Vol. 175, No. 10. pp. 6368-6377.
@article{ddadd32ce9084e36a05400ac12c8f641,
title = "Evaluation of OX40 ligand as a costimulator of human antiviral memory CD8 T cell responses: Comparison with B7.1 and 4-1BBL",
abstract = "CTL are important effectors of antiviral immunity. Designing adjuvants that can induce strong cytotoxic T cell responses in humans would greatly improve the effectiveness of an antiviral vaccination or therapeutic strategy. Recent evidence suggests that, in addition to its well-established role in costimulation of CD4 T cell responses, OX40L (CD134) can directly costimulate mouse CD8 T cells. In this study, we evaluated the role of OX40L in costimulation of human antiviral CD8 T cell responses and compared it with two other important costimulators, B7.1 (CD80) and 4-1BBL (CD137L). Delivery of OX40L to human monocytes using a recombinant replication-defective adenovirus led to greater expansion, up-regulation of perforin, enhanced cytolytic activity, and increased numbers of IFN-γ-and TNF-α-producing antiviral memory CD8 T cells in cultures of total T eels. Synergistic or additive effects were observed when OX40L costimulation was combined with 4-1BBL (CD137L) or B7.1 (CD80) costimulation. In total T cell cultures, at low Ag dose, 4-1BBL provided the most potent costimulus for influenza-specific CD8 T cell expansion, followed by B7.1 (CD80) and then OX40L. For isolated CD8 T cells, 4-1BBL was also the most consistent costimulator, followed by B7.1. In contrast, OX40L showed efficacy in direct activation of memory CD8 T cells in only one of seven donors. Thus, OX40L costimulates human antiviral memory CD8 T cell responses largely through indirect effects and can enhance anti-influenza, anti-EBV, and anti-HIV responses, particularly in combination with 4-1BBL or B7.",
author = "Lena Serghides and Jacob Bukczynski and Tao Wen and Chao Wang and Routy, {Jean Pierre} and Boulassel, {Mohamed Rachid} and Sekaly, {Rafick Pierre} and Mario Ostrowski and Bernard, {Nicole F.} and Watts, {Tania H.}",
year = "2005",
month = "11",
day = "15",
language = "English",
volume = "175",
pages = "6368--6377",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "10",

}

TY - JOUR

T1 - Evaluation of OX40 ligand as a costimulator of human antiviral memory CD8 T cell responses

T2 - Comparison with B7.1 and 4-1BBL

AU - Serghides, Lena

AU - Bukczynski, Jacob

AU - Wen, Tao

AU - Wang, Chao

AU - Routy, Jean Pierre

AU - Boulassel, Mohamed Rachid

AU - Sekaly, Rafick Pierre

AU - Ostrowski, Mario

AU - Bernard, Nicole F.

AU - Watts, Tania H.

PY - 2005/11/15

Y1 - 2005/11/15

N2 - CTL are important effectors of antiviral immunity. Designing adjuvants that can induce strong cytotoxic T cell responses in humans would greatly improve the effectiveness of an antiviral vaccination or therapeutic strategy. Recent evidence suggests that, in addition to its well-established role in costimulation of CD4 T cell responses, OX40L (CD134) can directly costimulate mouse CD8 T cells. In this study, we evaluated the role of OX40L in costimulation of human antiviral CD8 T cell responses and compared it with two other important costimulators, B7.1 (CD80) and 4-1BBL (CD137L). Delivery of OX40L to human monocytes using a recombinant replication-defective adenovirus led to greater expansion, up-regulation of perforin, enhanced cytolytic activity, and increased numbers of IFN-γ-and TNF-α-producing antiviral memory CD8 T cells in cultures of total T eels. Synergistic or additive effects were observed when OX40L costimulation was combined with 4-1BBL (CD137L) or B7.1 (CD80) costimulation. In total T cell cultures, at low Ag dose, 4-1BBL provided the most potent costimulus for influenza-specific CD8 T cell expansion, followed by B7.1 (CD80) and then OX40L. For isolated CD8 T cells, 4-1BBL was also the most consistent costimulator, followed by B7.1. In contrast, OX40L showed efficacy in direct activation of memory CD8 T cells in only one of seven donors. Thus, OX40L costimulates human antiviral memory CD8 T cell responses largely through indirect effects and can enhance anti-influenza, anti-EBV, and anti-HIV responses, particularly in combination with 4-1BBL or B7.

AB - CTL are important effectors of antiviral immunity. Designing adjuvants that can induce strong cytotoxic T cell responses in humans would greatly improve the effectiveness of an antiviral vaccination or therapeutic strategy. Recent evidence suggests that, in addition to its well-established role in costimulation of CD4 T cell responses, OX40L (CD134) can directly costimulate mouse CD8 T cells. In this study, we evaluated the role of OX40L in costimulation of human antiviral CD8 T cell responses and compared it with two other important costimulators, B7.1 (CD80) and 4-1BBL (CD137L). Delivery of OX40L to human monocytes using a recombinant replication-defective adenovirus led to greater expansion, up-regulation of perforin, enhanced cytolytic activity, and increased numbers of IFN-γ-and TNF-α-producing antiviral memory CD8 T cells in cultures of total T eels. Synergistic or additive effects were observed when OX40L costimulation was combined with 4-1BBL (CD137L) or B7.1 (CD80) costimulation. In total T cell cultures, at low Ag dose, 4-1BBL provided the most potent costimulus for influenza-specific CD8 T cell expansion, followed by B7.1 (CD80) and then OX40L. For isolated CD8 T cells, 4-1BBL was also the most consistent costimulator, followed by B7.1. In contrast, OX40L showed efficacy in direct activation of memory CD8 T cells in only one of seven donors. Thus, OX40L costimulates human antiviral memory CD8 T cell responses largely through indirect effects and can enhance anti-influenza, anti-EBV, and anti-HIV responses, particularly in combination with 4-1BBL or B7.

UR - http://www.scopus.com/inward/record.url?scp=27744446078&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27744446078&partnerID=8YFLogxK

M3 - Article

C2 - 16272289

AN - SCOPUS:27744446078

VL - 175

SP - 6368

EP - 6377

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 10

ER -