Stimulation through very late antigen‐4 and ‐5 improves the multifunctionality and memory formation of CD8+ T cells. Issue 6 (11th May 2014)

• Record Type: Journal Article
• Authors: Hosoi, Hayato; Ikeda, Hiroaki; Imai, Naoko; Amaike, Chisaki; Wang, Linan; Orito, Yuki; Yamane, Makiko; Ueno, Hiroaki; Ideno, Mitsuko; Nukaya, Ikuei; Enoki, Tatsuji; Mineno, Junichi; Takesako, Kazutoh; Hirano, Satoshi; Shiku, Hiroshi
• Is Part Of: European journal of immunology. Volume 44:Issue 6(2014:Jun.)
• Page Start: 1747
• Page End: 1758
• Publication Date: 2014-05-11
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201343969
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>T cells express multiple integrin molecules. The significance of signaling through these molecules on acquisition of T‐cell effector functions and memory formation capacity remains largely unknown. Moreover, the impact of stimulation through these signals on the generation of T cells for adoptive immunotherapy has not been elucidated. In this study, using a recombinant fragment of fibronectin, CH‐296, we demonstrated that stimulation via very late Ag (VLA)‐4 and VLA‐5 in human and BALB/c mouse CD8⁺ T cells, in combination with TCR stimulation, enhances effector multifunctionality and in vivo memory formation. Using TCR‐transgenic mouse‐derived CD8⁺ T cells expressing TCR specific for the syngeneic CMS5 fibrosarcoma‐derived tumor Ag, we showed that stimulation by CH‐296 improved the ability of tumor‐specific CD8⁺ T cells to inhibit CMS5 tumor growth when adoptively transferred into hosts with progressing tumors. Improved antitumor effects were associated with decreased infiltration of Foxp3⁺CD4⁺ Treg cells in tumors. These results suggest that stimulation via VLA‐4 and VLA‐5 modulates the qualities of effector T cells and could potentially increase the efficacy of adoptive therapy against cancer.</p> </abstract>