Both authors contributed equally to this work.
Human mucosal CD4+ T cells but not blood CD4+ T cells respond vigorously towards CD28 engagement
Version of Record online: 2 MAR 2012
© 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology
Clinical & Experimental Immunology
Volume 168, Issue 1, pages 87–94, April 2012
How to Cite
Schröder-Braunstein, J., Pavlov, V., Giese, T., Heidtmann, A., Wentrup, S., Lasitschka, F., Winter, J., Ulrich, A., Engelke, A., Al Saeedi, M. and Meuer, S. (2012), Human mucosal CD4+ T cells but not blood CD4+ T cells respond vigorously towards CD28 engagement. Clinical & Experimental Immunology, 168: 87–94. doi: 10.1111/j.1365-2249.2011.04539.x
E-mail address of senior author: email@example.com
- Issue online: 2 MAR 2012
- Version of Record online: 2 MAR 2012
- Accepted manuscript online: 28 NOV 2011 11:13AM EST
- Accepted for publication 21 November 2011
- human lamina propria T lymphocytes;
- PI3-kinase pathway
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.