Faculty Collaboration Database

Murine CD8 lymphocyte expansion in vitro by artificial antigen-presenting cells expressing CD137L (4-1BBL) is superior to CD28, and CD137L expressed on neuroblastoma expands CD8 tumour-reactive effector cells in vivo. Immunology 2004 May;112(1):105-16

Date

04/21/2004

Pubmed ID

15096190

Pubmed Central ID

PMC1782467

DOI

10.1111/j.1365-2567.2004.01853.x

Scopus ID

2-s2.0-2342604967 (requires institutional sign-in at Scopus site)   30 Citations

Abstract

The ability to expand tumour-infiltrating lymphocytes in vitro has been greatly enhanced by the use of antigen-independent mechanisms of immune cell costimulation. We have produced human, using the K562 cell line, and murine, using YAC-1 cells, artificial antigen presenting cells (aAPC) and demonstrate that these cell types stimulate murine lymphocyte populations in distinct ways. Using aAPC that have been transfected with CD137L (4-1BBL) and CD32 (FcRgammaII), as a means to bind anti-CD3 and anti-CD28 antibody, we found that CD4 cells preferentially expanded in vitro with K562 aAPC, while CD8 cells expanded with both K562 and YAC-1 aAPC. Co-stimulation mediated by CD137L on aAPC was superior to that mediated by anti-CD28 antibody. This was seen in both long and short-term expansion assays, and by the rapid induction of a CD8+ DX5+ population. DX5 serves, under these in vitro conditions, as a general marker for lymphocyte activation. In vivo, the superiority of CD137L was demonstrated by the induction of T helper 1 effectors seen in freshly isolated splenocytes from mice immunized with CD137L-expressing neuroblastoma tumour vaccines. The ability to stimulate a strong CD8 CTL response in vivo correlated with the induction of a DX5+ cell population in splenocytes with a memory-effector phenotype. The presence of this unique DX5+ cell population, phenotypically distinct with regards to CD69 and CD62L expression from DX5+ cells induced by aAPC in vitro, may be associated with the ability of CD137L to induce strong anti-tumour immunity.

Author List

Yan X, Johnson BD, Orentas RJ

Author

Bryon D. Johnson PhD Adjunct Professor in the Medicine department at Medical College of Wisconsin

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

4-1BB Ligand
Animals
Antigen-Presenting Cells
Antigens, CD
CD28 Antigens
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cancer Vaccines
Cell Division
Cytotoxicity, Immunologic
Humans
Immunophenotyping
Interferon-gamma
K562 Cells
Ligands
Male
Mice
Mice, Inbred A
Neuroblastoma
Receptors, Nerve Growth Factor
Receptors, Tumor Necrosis Factor
Spleen
Tumor Necrosis Factor Receptor Superfamily, Member 9
Tumor Necrosis Factor-alpha