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CD40 ligand is essential for generation of specific cytotoxic T cell responses in RNA-pulsed dendritic cell immunotherapy.

Publication ,  Journal Article
Onaitis, MW; Kalady, MF; Emani, S; Abdel-Wahab, Z; Tyler, DS; Pruitt, SK
Published in: Surgery
August 2003

BACKGROUND: Dendritic cell (DC)-based immunotherapy is a promising form of adjuvant therapy for high-risk tumors. DCs transfected with tumor-associated antigens are capable of stimulating antigen-specific T cells, but cytolytic responses have been disappointing. Activation of DC surface CD40 influences DC cytokine production, particularly that of interleukin (IL)-12, which favors a Th1 (cytotoxic) helper T cell response. This study evaluated the effects of exogenous soluble CD40 ligand (sCD40L) on RNA-transfected DC preparations and their subsequent ability to generate antimelanoma cytolytic T cells. METHODS: Human monocyte-derived DCs were cultured and transfected with mRNA encoding full-length melanoma-associated antigen, Mart-1, and matured with and without sCD40L. DC IL-12 secretion and the ability to stimulate naïve T cells were assessed by enzyme-linked immunosorbent assay (ELISA), tetramer analysis, Elispot, and (51)Cr release assay. RESULTS: Mature DCs stimulated with sCD40L secreted higher levels of IL-12 compared with immature DCs and DCs matured without sCD40L (P <.001). DCs treated with sCD40L generated a greater number of antigen-specific T cells (P <.05) by tetramer and Elispot analyses, and yielded specific T cells with significant cytotoxicity against HLA-matched melanoma cell lines. CONCLUSIONS: CD40L augments DC IL-12 secretion and is essential to potentiate specific antimelanoma cytolytic responses stimulated by the Mart-1 antigen. sCD40L should be considered a crucial adjuvant in DC preparations for RNA-based DC vaccine therapies.

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Published In

Surgery

DOI

ISSN

0039-6060

Publication Date

August 2003

Volume

134

Issue

2

Start / End Page

300 / 305

Location

United States

Related Subject Headings

  • Transfection
  • T-Lymphocytes, Regulatory
  • T-Lymphocytes, Cytotoxic
  • Surgery
  • RNA, Messenger
  • Neoplasm Proteins
  • Melanoma
  • MART-1 Antigen
  • Interleukin-12
  • Immunotherapy
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Onaitis, M. W., Kalady, M. F., Emani, S., Abdel-Wahab, Z., Tyler, D. S., & Pruitt, S. K. (2003). CD40 ligand is essential for generation of specific cytotoxic T cell responses in RNA-pulsed dendritic cell immunotherapy. Surgery, 134(2), 300–305. https://doi.org/10.1067/msy.2003.240
Onaitis, Mark W., Matthew F. Kalady, Sirisha Emani, Zeinab Abdel-Wahab, Douglas S. Tyler, and Scott K. Pruitt. “CD40 ligand is essential for generation of specific cytotoxic T cell responses in RNA-pulsed dendritic cell immunotherapy.Surgery 134, no. 2 (August 2003): 300–305. https://doi.org/10.1067/msy.2003.240.
Onaitis MW, Kalady MF, Emani S, Abdel-Wahab Z, Tyler DS, Pruitt SK. CD40 ligand is essential for generation of specific cytotoxic T cell responses in RNA-pulsed dendritic cell immunotherapy. Surgery. 2003 Aug;134(2):300–5.
Onaitis, Mark W., et al. “CD40 ligand is essential for generation of specific cytotoxic T cell responses in RNA-pulsed dendritic cell immunotherapy.Surgery, vol. 134, no. 2, Aug. 2003, pp. 300–05. Pubmed, doi:10.1067/msy.2003.240.
Onaitis MW, Kalady MF, Emani S, Abdel-Wahab Z, Tyler DS, Pruitt SK. CD40 ligand is essential for generation of specific cytotoxic T cell responses in RNA-pulsed dendritic cell immunotherapy. Surgery. 2003 Aug;134(2):300–305.
Journal cover image

Published In

Surgery

DOI

ISSN

0039-6060

Publication Date

August 2003

Volume

134

Issue

2

Start / End Page

300 / 305

Location

United States

Related Subject Headings

  • Transfection
  • T-Lymphocytes, Regulatory
  • T-Lymphocytes, Cytotoxic
  • Surgery
  • RNA, Messenger
  • Neoplasm Proteins
  • Melanoma
  • MART-1 Antigen
  • Interleukin-12
  • Immunotherapy