Extracellular matrix conditions T cells for adhesion to tissue interstitium

Area of Science:

• Immunology
• Cell Biology
• Biochemistry

Background:

• Peripheral blood T cells (PBT) show increased beta(1) integrin expression upon activation, enhancing adhesion to the extracellular matrix (ECM).
• Regulation of integrin function on tissue-resident T cells within the interstitial ECM remains poorly understood.

Purpose of the Study:

• To investigate integrin expression, affinity, and avidity on intestinal lamina propria T cells.
• To compare the adhesive properties of tissue T cells with peripheral blood T cells (PBT).
• To identify extrinsic factors in the tissue microenvironment that regulate T cell adhesion.

Main Methods:

• Isolation and functional analysis of T cells from intestinal lamina propria and peripheral blood.
• Assessment of integrin-mediated adhesion to collagen, fibronectin, and cell-derived ECM.
• Activation of PBT in the presence of ECM components (fibronectin, collagen).

Main Results:

• Tissue T cells exhibit distinct, functionally active integrin profiles with enhanced adhesion to ECM components compared to PBT.
• Lamina propria T cells preferentially bind collagen, while PBT lymphoblasts bind fibronectin in a complex matrix.
• Activation of PBT with fibronectin or collagen rapidly induces a tissue T cell-like adhesive phenotype.

Conclusions:

• The tissue ECM microenvironment actively instructs T cells, imprinting them with a specific adhesive phenotype.
• This process involves the regulation of integrin expression and usage, facilitating tissue-specific T cell interactions.
• Extrinsic factors within the tissue microenvironment play a crucial role in converting circulating T cells into tissue-resident cells.