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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.I

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.

Authors+Show Affiliations

Department of Pediatrics, Section of Hematology-Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15096190

Citation

Yan, Xiaocai, et al. "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, vol. 112, no. 1, 2004, pp. 105-16.
Yan X, Johnson BD, Orentas RJ. 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;112(1):105-16.
Yan, X., Johnson, B. D., & Orentas, R. J. (2004). 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, 112(1), 105-16.
Yan X, Johnson BD, Orentas RJ. 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;112(1):105-16. PubMed PMID: 15096190.
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TY - JOUR T1 - 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. AU - Yan,Xiaocai, AU - Johnson,Bryon D, AU - Orentas,Rimas J, PY - 2004/4/21/pubmed PY - 2004/6/23/medline PY - 2004/4/21/entrez SP - 105 EP - 16 JF - Immunology JO - Immunology VL - 112 IS - 1 N2 - 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. SN - 0019-2805 UR - https://www.unboundmedicine.com/medline/citation/15096190/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_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=15096190.ui DB - PRIME DP - Unbound Medicine ER -