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Intestinal dendritic cells increase T cell expression of alpha4beta7 integrin
Andrew J Stagg1, Michael A Kamm, Stella C Knight
1Antigen Presentation Research Group, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Harrow, GB. a.stagg@ic.ac.uk
European Journal of Immunology
|May 1, 2002
Summary
Antigen-presenting cells, specifically dendritic cells (DC), influence lymphocyte homing. Mesenteric lymph node (MLN) DC promote higher levels of alpha4beta7 integrin expression in T cells compared to peripheral lymph node (PLN) DC.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Integrin alpha4beta7 plays a crucial role in lymphocyte homing to mucosal tissues by binding to MAdCAM-1.
- The subset of circulating memory cells expressing high levels of alpha4beta7 (alpha4beta7(hi)) in humans are thought to be primed in mucosal tissues.
- The factors governing the differentiation of naive T cells into alpha4beta7(hi) or alpha4beta7(-) cells remain unclear, with potential involvement of the activating antigen-presenting cell (APC).
Purpose of the Study:
- To investigate the role of APCs in the induction of alpha4beta7 integrin expression on T cells.
- To determine if the origin of APCs (mucosal vs. peripheral) influences alpha4beta7 expression levels.
- To understand how APCs shape T cell homing potential during immune activation.
Main Methods:
- Activation of mouse T cells using soluble anti-CD3 stimulation in the presence of accessory cells.
- Flow cytometry analysis to quantify alpha4beta7 integrin expression on T cells.
- Comparison of T cell activation and alpha4beta7 induction using dendritic cells (DC) from mesenteric lymph nodes (MLN) versus peripheral lymph nodes (PLN).
Main Results:
- Activation of T cells with anti-CD3 induced a subpopulation of alpha4beta7(hi) cells in a cell cycle- and accessory cell-dependent manner.
- A small percentage (approx. 1.5%) of T cells differentiated into alpha4beta7(hi) cells after culture.
- MLN DC induced significantly higher proportions and numbers of alpha4beta7(hi) T cells compared to PLN DC, regardless of the T cell source.
- Peyer's patch DC generated intermediate levels of alpha4beta7(hi) cells.
Conclusions:
- Dendritic cells (DC) play a significant role in regulating T cell homing potential by influencing alpha4beta7 integrin expression.
- The anatomical origin of DC (MLN vs. PLN) dictates their capacity to induce alpha4beta7(hi) T cells.
- These findings highlight a mechanism by which APCs can shape adaptive immune responses by directing lymphocyte trafficking to specific tissues.