ICOS Costimulation Differentially Affects T Cells in Secondary Lymphoid Organs and Inflamed Tissues.
Dana Vu VanLaura BauerRichard A KroczekAndreas HutloffPublished in: American journal of respiratory cell and molecular biology (2019)
B-cell interaction with follicular helper T cells and subsequent differentiation of B cells into high-affinity APCs normally takes place in secondary lymphoid organs. The costimulator ICOS plays a key role in this process and is therefore considered as an attractive target to modulate exaggerated B-cell responses in autoimmune or allergic diseases. Inflamed tissues were recently recognized as additional sites of active T-cell/B-cell interaction. To analyze whether ICOS costimulation is also important there, we employed a mouse airway inflammation model that allows direct comparison of immune reactions in the lung-draining lymph node and the lung tissue as well as assessment of the relative importance of dendritic cells versus B cells as APCs. In both organs, ICOS regulated the pool size of antigen-specific T and B cells and B-cell differentiation into germinal center(-like) cells but not into antibody-secreting cells. In the lymph node, lack of ICOS costimulation drastically reduced the frequency of T follicular helper cells but did not affect production of T-helper cell type 2 (Th2) cytokines. Vice versa in the lung tissue, ICOS did not change PD-1 expression on infiltrating T cells but regulated Th2 cytokine production, a process for which ICOS ligand expression on B cells was of particular importance. Taken together, the results of this study show that ICOS differentially regulates effector T cells in secondary lymphoid organs and inflamed tissues but that blockade of the ICOS pathway is suitable to target T cell-dependent B cell responses at both sites.
Keyphrases
- dendritic cells
- lymph node
- regulatory t cells
- induced apoptosis
- gene expression
- cell cycle arrest
- immune response
- neoadjuvant chemotherapy
- multiple sclerosis
- cell death
- oxidative stress
- radiation therapy
- signaling pathway
- early stage
- binding protein
- squamous cell carcinoma
- endoplasmic reticulum stress
- drug induced
- atopic dermatitis