Human mucosal CD4+ T cells but not blood CD4+ T cells respond vigorously towards CD28 engagement

• Verfasst von: Schröder-Braunstein, Jutta [VerfasserIn]
• Verfasst von: Pavlov, Vladimir [VerfasserIn]
• Verfasst von: Giese, Thomas [VerfasserIn]
• Verfasst von: Heidtmann, Antje [VerfasserIn]
• Verfasst von: Wentrup, Sabine [VerfasserIn]
• Verfasst von: Lasitschka, Felix [VerfasserIn]
• Verfasst von: Ulrich, Alexis [VerfasserIn]
• Verfasst von: Engelke, Antonia [VerfasserIn]
• Verfasst von: Saeedi, Mohammed al [VerfasserIn]
• Verfasst von: Meuer, Stefan [VerfasserIn]
• Titel: Human mucosal CD4+ T cells but not blood CD4+ T cells respond vigorously towards CD28 engagement
• Verf.angabe: J. Schröder-Braunstein, V. Pavlov, T. Giese, A. Heidtmann, S. Wentrup, F. Lasitschka, J. Winter, A. Ulrich, A. Engelke, M. Al Saeedi and S. Meuer
• Jahr des Originals: 2011
• Umfang: 8 S.
• Fussnoten: Published online: 28 November 2011 ; Gesehen am 11.04.2018
• Titel Quelle: Enthalten in: Clinical and experimental immunology
• Jahr Quelle: 2012
• Band/Heft Quelle: 168(2012), 1, S. 87-94
• ISSN Quelle: 1365-2249
• DOI: doi:10.1111/j.1365-2249.2011.04539.x
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 157190591X

Abstract

Human lamina propria T lymphocytes (LPT) possess functional properties profoundly different from those of peripheral blood T lymphocytes (PBT). While they are characterized by a low proliferative response to T cell receptor (TCR)/CD3 stimulation in vitro their responsiveness to activation through the ‘co-stimulatory’ CD2-receptor is enhanced when compared to PBT. In this study, we demonstrate that engagement of another co-stimulatory receptor on both LPT and PBT, namely CD28, by a single monoclonal antibody (mAb), respectively, strongly activates the former but not the latter through a PI3-kinase dependent signalling pathway leading to the production of inflammatory cytokines such as interleukin (IL)-2, tumour necrosis factor (TNF)-α, interferon (IFN)-γ and granulocyte-macrophage colony-stimulating factor (GM-CSF). In addition to the high sensitivity of LPT to CD2 stimulation, this finding supports the notion that ‘non-specific/innate’ mechanisms to activate T lymphocytes play a predominant role vis-à-vis‘TCR driven/adaptive’ responses in the intestinal mucosa. Furthermore, it suggests that results from preclinical tests for therapeutic antibodies performed with human blood derived T cells are probably insufficient to predict reactivities of tissue-resident immune cells, which - given their quantitative predominance - may critically determine the in-vivo response to such compounds.