Faculty Collaboration Database

Murine splenic CD4⁺ T cells, induced by innate immune cell interactions and secreted factors, develop antileukemia cytotoxicity. Cancer Immunol Res 2014 Nov;2(11):1113-24

Date

08/27/2014

Pubmed ID

25154710

DOI

10.1158/2326-6066.CIR-13-0208

Scopus ID

2-s2.0-84940100387 (requires institutional sign-in at Scopus site)   11 Citations

Abstract

Inciting the cellular arm of adaptive immunity has been the fundamental goal of cancer immunotherapy strategies, specifically focusing on inducing tumor antigen-specific responses by CD8(+) cytotoxic T lymphocytes (CTL). However, there is an emerging appreciation that the cytotoxic function of CD4(+) T cells can be effective in a clinical setting. Harnessing this potential will require an understanding of how such cells arise. In this study, we use an IL12-transduced variant of the 70Z/3 leukemia cell line in a B6D2F1 (BDF1) murine model system to reveal a novel cascade of cells and soluble factors that activate anticancer CD4(+) killer cells. We show that natural killer T cells play a pivotal role by activating dendritic cells in a contact-dependent manner; soluble products of this interaction, including MCP-1, propagate the activation signal, culminating in the development of CD4(+) CTLs that directly mediate an antileukemia response while also orchestrating a multipronged attack by other effector cells. A more complete picture of the conditions that induce such a robust response will allow us to capitalize on CD4(+) T-cell plasticity for maximum therapeutic effect.

Author List

Nelles ME, Moreau JM, Furlonger CL, Berger A, Medin JA, Paige CJ

Author

Jeffrey A. Medin PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
CD4-Positive T-Lymphocytes
Cell Communication
Cell Line, Tumor
Coculture Techniques
Dendritic Cells
Female
Flow Cytometry
Immunity, Innate
Immunotherapy
Leukemia
Lymphocyte Activation
Mice
Natural Killer T-Cells
Reverse Transcriptase Polymerase Chain Reaction
Spleen
T-Lymphocytes, Cytotoxic