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Induction of a VLA-2 (CD49b)-expressing effector T cell population by a cell-based neuroblastoma vaccine expressing CD137L.
J Immunol. 2008 Oct 01; 181(7):4621-31.JI

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 (T(EM)) response arises in which a large number of the T(EM) express the alpha-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 T(EM) 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.

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

18802064

Citation

Yan, Xiaocai, et al. "Induction of a VLA-2 (CD49b)-expressing Effector T Cell Population By a Cell-based Neuroblastoma Vaccine Expressing CD137L." Journal of Immunology (Baltimore, Md. : 1950), vol. 181, no. 7, 2008, pp. 4621-31.
Yan X, Johnson BD, Orentas RJ. Induction of a VLA-2 (CD49b)-expressing effector T cell population by a cell-based neuroblastoma vaccine expressing CD137L. J Immunol. 2008;181(7):4621-31.
Yan, X., Johnson, B. D., & Orentas, R. J. (2008). Induction of a VLA-2 (CD49b)-expressing effector T cell population by a cell-based neuroblastoma vaccine expressing CD137L. Journal of Immunology (Baltimore, Md. : 1950), 181(7), 4621-31.
Yan X, Johnson BD, Orentas RJ. Induction of a VLA-2 (CD49b)-expressing Effector T Cell Population By a Cell-based Neuroblastoma Vaccine Expressing CD137L. J Immunol. 2008 Oct 1;181(7):4621-31. PubMed PMID: 18802064.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induction of a VLA-2 (CD49b)-expressing effector T cell population by a cell-based neuroblastoma vaccine expressing CD137L. AU - Yan,Xiaocai, AU - Johnson,Bryon D, AU - Orentas,Rimas J, PY - 2008/9/20/pubmed PY - 2008/12/25/medline PY - 2008/9/20/entrez SP - 4621 EP - 31 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 181 IS - 7 N2 - 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 (T(EM)) response arises in which a large number of the T(EM) express the alpha-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 T(EM) 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. SN - 1550-6606 UR - https://www.unboundmedicine.com/medline/citation/18802064/Induction_of_a_VLA_2__CD49b__expressing_effector_T_cell_population_by_a_cell_based_neuroblastoma_vaccine_expressing_CD137L_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=18802064 DB - PRIME DP - Unbound Medicine ER -