Induction of a VLA-2 (CD49b)-expressing effector T cell population by a cell-based neuroblastoma vaccine expressing CD137L

Xiaocai Yan, Bryon D. Johnson, Rimas J. Orentas

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

In malignancies where no universally expressed dominant Ag exists, the use of tumor cell-based vaccines has been proposed. We have modified a mouse neuroblastoma cell line to express either CD80 (B7.1), CD137L (4-1BBL), or both receptors on the tumor cell surface. Vaccines expressing both induce a strong T cell response that is unique in that among responding CD8 T cells, a T effector memory cell (TEM) response arises in which a large number of the TEM express the α-chain of VLA-2, CD49b. We demonstrate using both in vitro and in vivo assays that the CD49b+ CD8 T cell population is a far more potent antitumor effector cell population than nonfractionated CD8 or CD49b- CD8 T cells and that CD49b on vaccine-induced CD8 T cells mediates invasion of a collagen matrix. In in vivo rechallenge studies, CD49b+ T cells no longer expanded, indicating that CD49b TEM expansion is restricted to the initial response to vaccine. To demonstrate a mechanistic link between the expression of costimulatory molecules on the vaccine and CD49b on responding T cells, we stimulated naive T cells in vitro with artificial APC expressing different combinations of anti-CD3, anti-CD28, and CD137L. Although some mRNA encoding CD49b was induced by combining anti-CD3 with anti-CD28 or CD137L, the highest level was induced when all three signals were present. This indicates that CD49b expression results from additive costimulation and that the level of CD49b message serves as an indicator of the effectiveness of T cell activation by a cell-based vaccine.

Original languageEnglish (US)
Pages (from-to)4621-4631
Number of pages11
JournalJournal of Immunology
Volume181
Issue number7
DOIs
StatePublished - Oct 1 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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